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INFUSE BONE GRAFT/LT-CAGE
LUMBAR TAPERED FUSION DEVICE
®
Open Surgical Technique
®
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Table of Contents
Preoperative Templating
2
Intraoperative Preparation
3
Step 1
Midline Marking and Alignment
4
Midline Marking and Preparation of the Disc Space
5
Step 2
Distraction and Outer Sleeve Placement
7
Step 3
Vertebral End-plate Reaming
10
Step 4
Preparation of INFUSE® Bone Graft Component
14
Step 5
Device Implantation
20
Single Barrel Technique Steps
23
Lumbar Tapered Instruments
24
1
2
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Preoperative Templating
Once the appropriate spinal level has been identified, the proper size device must be selected. Templates are
available to facilitate proper device selection from plain radiographs, CT, or MRI scans. These Templates are
available in appropriate reduction or magnification ratios for radiographs and CT or MRI scans (Figure 1). To
determine the magnification of a CT or MRI scan, match the scale on the Template with the scale on the CT
or MRI scan. Example Templates are shown below.
These Templates allow the surgeon to measure normal, adjacent disc space height, and determine
intraoperative distraction height. In using the Templates, the physician must ensure that the devices remain
within the lateral borders of the intervertebral disc space. Device length, reaming depth, and countersink may
also be assessed preoperatively using the Templates.
Once the device size is determined, note the diameter of the leading end. This diameter is used to reference
the corresponding instrumentation. A color-coding system is used to differentiate each of the leading diameters.
14mm – Red
16mm – Green
18mm – Blue
LT-CAGE® Lumbar Tapered Fusion Device Templates
LT Distractors and Cages
∞
∞
∞
∞
∞
∞
Figure 1
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Intraoperative Preparation
Intraoperatively, the patient is placed on the operating table in a supine position. Compression stockings
should be placed on the patient. General anesthesia with endotracheal intubation is administered.
The lumbar spine may be approached through either a transperitoneal or an anterior retroperitoneal
exposure (Figure 2). The amount of great vessel release and retraction should be limited to that required
for insertion of the instruments and devices. At the L2 – L3 and L3 – L4 levels, a standard approach is used to
mobilize the vessels and access the anterior spine. At the L4 – L5 level, the iliolumbar and segmental vessels
should be identified and ligated if necessary in order to achieve adequate mobilization of the great vessels.
At L5 – SI, the middle sacral artery is typically ligated and divided. Care should be taken at L5 – SI to only use
blunt dissection in order to minimize injury to the presacral neural plexus.
Figure 2
3
4
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Midline Marking and Alignment
The center of the disc should be located and marked with the assistance of both AP and lateral
fluoroscopy. Accurate identification of the midline is essential for the successful implantation of two
LT-CAGE® Device components.
Attach the Centering Pin to the Centering Pin Template Shaft and place at the center of the disc (Figure 3).
The position is checked with AP fluoroscopy and adjusted as needed. Since a block discectomy is to be
performed, marks are placed at midline on the vertebral bodies both cephalad and caudal to the Centering
Pin (Figure 3A). A lateral fluoroscopic check is helpful in confirming the targeted lumbar level (Figure 3B).
Tip: Mark the vertebral bodies both cephalad and
caudal to the centering pin.
Figure 3
Figure 3A
Figure 3B
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Midline Marking and Preparation of the Disc Space
An en bloc discectomy is typically performed. This provides adequate space for insertion of the Distractors,
ensuring that the disc is not displaced during insertion. The disc removal instrumentation will simultaneously
remove the required volume of remaining disc and prepare the adjacent vertebral bodies for the threaded
device. Anterior osteophytes should be removed to ensure accurate seating of the instrumentation against
the vertebral bodies.
Remove the Centering Pin from the Centering Pin Template Shaft and attach the appropriate size
colored Template (14mm, 16mm, 18mm). Position the colored Template so the central notch is aligned
with the midline.
Holding the appropriate colored Template against the disc space, identify and mark the lateral margins of the
block discectomy (Figure 4). Incise the annulus sharply. Use a Pituitary Rongeur to remove the nucleus pulposus.
The instrumentation used to implant the LT-CAGE® Device component centralizes within the annular window,
therefore, it is extremely important to properly create the annular window by centering the Template on the
midline markings and incising the annulus along the lateral edges of the Template.
Tip: Remove any anterior osteophytes to
ensure the instrumentation seats flush
against the vertebral bodies.
Figure 4
5
6
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
­­Midline Marking and Preparation of the Disc Space (continued)
Curettes are used to remove the cartilaginous end plates. These steps are performed under direct
visualization, taking care not to perforate posteriorly or laterally. Lateral fluoroscopy may be used to confirm
the extent of the posterior disc removal through visualization of discectomy instruments. Use care to avoid
exceeding the lateral margins defined by the block discectomy Template annulus anterolaterally (Figure 5).
After completion of the block discectomy, the anterolateral annulus remains intact and acts to enhance
device stability (Figure 6).
Continue the procedure utilizing specific instrumentation for the appropriate diameter devices.
Figure 5
Figure 6
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Distraction and Outer Sleeve Placement
Sequential distraction is carried out using the Starter Distractor Driver and sized Distractor
Tips (Figure 7). The Starter Distractors are sequentially driven into the disc space at
midline, acting to develop the disc space height in preparation for the placement
of the Distractor Assembly.
The Starter Distractor sizes included in the general instrument tray are:
6mm
8mm
10mm
12mm
Figure 7
Mating Distractor Shafts (Figure 8) are located in the size-specific trays.
The following distraction heights are provided with the corresponding
instrument sets:
14mm instruments = 10mm Distraction
16mm instruments = 12mm Distraction
18mm instruments = 14mm Distraction
Tip: In addition to sequential distraction of the
disc space, the Starter Distractors can help
confirm the final distraction height.
Figure 8
7
8
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Distraction and Outer Sleeve Placement (continued)
If appropriate, the Starter Distraction step may be eliminated. Final distraction to the selected height follows.
The radiolucent Distractors are intended to provide contact with the end plates, resulting in uniform annular
tensioning and disc space height restoration.
Mate the Cylindrical and C-style Distractors and slide into the Double Barrel Sleeve. With the proximal end
of the Distraction Shafts slightly proud, slide the Distraction Driver Cap along the slot in the Outer Sleeve,
capturing the Distraction Shafts.
Insert the radiolucent Distractor Tips into the disc space. Verify midline placement by referencing the marks
created in Step 1. Impact the Distractor Driver Cap until the Distractor Tips are fully seated (Figure 9).
Radiographic markers in the Distractor Tips will help determine the position of the Distractors while seating.
Remain parallel to the end plates during insertion and verify with lateral fluoroscopy. The intact anterolateral
annulus will act to center the Distractors and reduce the lateral migration during impaction. Remove the
Distractor Driver Cap by sliding the cap off the proximal end of the Distractors and Outer Sleeve.
Tip: Make sure the Distractor Driver
Cap captures both the Distractors
and the Outer Sleeve.
Figure 9
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Distraction and Outer Sleeve Placement (continued)
Place the Driver Cap and impact the Outer Sleeve until fully seated (Figure 10).
Fluoroscopic control is helpful in assessing distraction height and orientation of the Distractors. The
Distractors act as a centering and alignment guide for the procedure; it is essential that they are
located properly.
Tip: Prior to fully seating the Outer Sleeve, all vascular
structures should be accurately identified and adequately
retracted. Intraoperative fluoroscopy is useful in confirming
that the Outer Sleeve is fully seated against the vertebral
bodies and properly oriented within the disc space. The
Outer Sleeve Barrel extensions are intended to assist in
keeping soft tissue and vascular structures from slipping
under the lateral margin of the Outer Sleeve.
Figure 10
9
10
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Vertebral End-plate Reaming
With the Double Barrel Outer Sleeve fully seated, use the Instrument
Remover to carefully remove the Cylindrical Distractor to allow a
cylindrical working channel (Figure 11). The C-styled Distractor remains
in place (Figure 11A and Figure 11B).
Tip: The Distractors are “keyed” so that the
Cylindrical Distractor must be removed first.
Figure 11A
Figure 11
Figure 11B
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Vertebral End-plate Reaming (continued)
The appropriately sized Hollow Reamer is used to prepare the disc space for placement of the LT-CAGE®
Device components.
Attach the Depth Stop to the Reamer. Hold the knurled sections of the Depth Stop and compress, allowing
the Depth Stop to move freely over the depth grooves. Slide the Depth Stop and orient the square window
to show the etched depth markings on the shaft of the Reamer (Figure 12). Release the proximal knurled
portion of the Depth Stop allowing it to lock in position. Verify that the desired depth compression appears in
the window.
NOTE: The Depth Stop may need to be rotated to view the depth setting in the window.
Tip: The appropriate Depth Stop setting should be
chosen based on the preoperative templating using
axial CT or MRI scans. The depth selected should
reflect the length of the threaded device and the
desired depth of countersinking.
Figure 12
11
12
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Open Surgical Technique
Vertebral End-plate Reaming (continued)
The T-handle (Figure 13) is attached. The Reamer is inserted into the Outer Sleeve and advanced in a
clockwise motion until the Depth Stop contacts the top of the Outer Sleeve (Figure 14). Several passes may
be taken (cleaning the Reamer after each pass) increasing the depth of penetration during each pass until the
Depth Stop makes contact with the top of the Outer Sleeve. Fluoroscopy should be used to verify the depth
of reaming (Figure 14A).
Figure 13
Tip: Any sensation of resistance to easy progression during reaming
should prompt removal and cleaning of the Reamer. When removing
the Reamer, a continued clockwise rotation should be performed to
aid in debris removal. The Reamer may be cleaned by wiping with a
moist lap sponge or by inserting the Reamer Clean Out Tool through
the clean out hole in the distal end of the Reamer.
Figure 14
Figure 14A
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Vertebral End-plate Reaming (continued)
Once the initial reaming is complete, insert the Reaming Plug into the Outer Sleeve (Figure 15 and Figure 15A).
Remove the C-styled Distractor and ream the contralateral side to the same depth.
Tip: Make sure both sides of the end plate
are reamed to the same depth.
Figure 15A
Figure 15
13
14
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Preparation of INFUSE ® Bone Graft Component
7510050 XX Small Kit (0.7cc)
(1) 5mL vial
(1) 1.05mg vial
Note: You will need to prepare a sterile and non-sterile field before
beginning product preparation.
Total preparation time: Allow at least 15 minutes for preparation
and an additional 15 minutes for protein to bind to collagen sponge.
(1) ACS ½" ∞ 2"
(1.25cm ∞ 5.08cm)
0.7cc graft volume
IN NON-STERILE FIELD
0.9mL
1
0.9mL
2
Observing proper sterile technique,
open the outer Absorbable Collagen
Sponge (ACS) package and place
the inner package containing the
one ½" ∞ 2" collagen sponge in the
sterile field. Open and place one of
the two 3mL syringe/needles in the
sterile field.
3
Using one needle and 3mL
syringe/needle, withdraw 0.9mL
of sterile water for injection.
4
Reconstitute the rhBMP-2 with
0.9mL of sterile water.
IN STERILE FIELD
0.7mL
on ACS
5
6
Open the inner ACS package
leaving the collagen sponge in
the plastic tray.
!
In the sterile field use the 3mL
syringe/needle to withdraw
0.7mL of reconstituted rhBMP‑2
from the vial held by the person
in the non-sterile field.
Allow wetted collagen sponges to stand for a minimum of 15 minutes.
Use within 2 hours. DO NOT use irrigation or suction near implanted device.
Note: During handling avoid excessive squeezing of the wetted sponge.
7
Uniformly distribute 0.7mL of
reconstituted rhBMP-2 on the
½" ∞ 2" collagen sponge. Inspect
the sponge. If dark particles are
observed, do not use and return
to sponsor.
Gently swirl (do not shake)
the rhBMP‑2 vial to ensure
adequate mixing. Inspect the
solution. If dark particles are
observed, do not use and return
to sponsor.
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Preparation of INFUSE ® Bone Graft Component (continued)
7510100 X Small Kit (1.4cc)
(2) 5mL vials
(2) 1.05mg vials
Note: You will need to prepare a sterile and non-sterile field before
beginning product preparation.
Total preparation time: Allow at least 15 minutes for preparation
and an additional 15 minutes for protein to bind to collagen sponge.
(1) ACS 1" ∞ 2"
(2.5cm ∞ 5.08cm)
1.4cc graft volume
IN NON-STERILE FIELD
0.9mL
1
2
Observing proper sterile
technique, open the outer
Absorbable Collagen Sponge
(ACS) package and place the inner
package containing the one 1" ∞ 2"
collagen sponge in the sterile field.
Open and place two 3mL syringes/
needles into the sterile field.
0.9mL
3
Using one of the two remaining
3mL syringes/needles
withdraw 0.9mL of sterile
water for injection.
4
Reconstitute one vial of the
rhBMP‑2 with 0.9mL of
sterile water.
Gently swirl (do not shake) the
rhBMP‑2 vial to ensure adequate
mixing. Using a second 3mL
syringe/needle repeat steps 2‑3
with the remaining vial of sterile
water and vial of rhBMP‑2. Inspect
the solution in both vials. If dark
particles are observed, do not use
and return to sponsor.
IN STERILE FIELD
0.7mL on
½ ACS
5
6
Open the inner ACS
package leaving the collagen
sponge in the plastic tray.
!
In the sterile field use
the 3mL syringe/needle
to withdraw 0.7mL of
reconstituted rhBMP‑2
from the first vial held
by the person in the
non-sterile field.
7
Uniformly distribute 0.7mL
of reconstituted rhBMP‑2
on half of the 1" ∞ 2"
collagen sponge.
Allow wetted collagen sponges to stand for a minimum of 15 minutes.
Use within 2 hours. DO NOT use irrigation or suction near implanted device.
Note: During handling avoid excessive squeezing of the wetted sponge.
0.7mL on
½ ACS
8
In the sterile field use the
second 3mL syringe/
needle to withdraw 0.7mL
of reconstituted rhBMP‑2
from the second vial held
by the person in the
non-sterile field.
9
Uniformly distribute 0.7mL of
reconstituted rhBMP‑2 on the
other half of the 1" ∞ 2" collagen
sponge. The total amount
of reconstituted rhBMP‑2
delivered to the sponge is
1.4mL. Inspect the sponge. If
dark particles are observed, do
not use and return to sponsor.
15
16
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Preparation of INFUSE ® Bone Graft Component (continued)
7510200 Small Kit (2.8cc)
(1) 5mL vial
(1) 4.2mg vial
Note: You will need to prepare a sterile and non-sterile field before
beginning product preparation.
Total preparation time: Allow at least 15 minutes for preparation
and an additional 15 minutes for protein to bind to collagen sponge.
(2) ACS 1" ∞ 2"
(2.54cm ∞ 5.08cm)
2.8cc graft volume
IN NON-STERILE FIELD
3.2mL
1
2
Observing proper sterile
technique, open the outer ACS
package and place the inner
package containing the two
1" ∞ 2" collagen sponges in the
sterile field. Open and place
one of the two 5mL syringes/
needles into the sterile field.
Using the other 5mL syringe/
needle, withdraw 3.2mL of
sterile water for injection.
3.2mL
3
4
Reconstitute the rhBMP‑2
with 3.2mL of sterile water.
Gently swirl (do not shake)
the rhBMP‑2 vial to ensure
adequate mixing.
IN STERILE FIELD
1.4mL on
1st ACS
5
6
Open the inner ACS package
leaving all collagen sponges in
the plastic tray.
!
In the sterile field use the 5mL
syringe/needle to withdraw 1.4mL
of reconstituted rhBMP‑2 from the
vial held by the person in the
non‑sterile field.
Allow wetted collagen sponges to stand for a minimum of 15 minutes.
Use within 2 hours. DO NOT use irrigation or suction near implanted device.
Note: During handling avoid excessive squeezing of the wetted sponge.
7
Uniformly distribute 1.4mL of
reconstituted rhBMP‑2 on one
of the 1" ∞ 2" collagen sponges.
1.4mL on
2nd ACS
8
Using the same 5mL syringe/
needle, repeat steps 6 and
7 for the remaining 1" ∞ 2"
collagen sponge.
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Preparation of INFUSE ® Bone Graft Component (continued)
7510400 Medium Kit (5.6cc)
(2) 5mL vials
(2) 4.2mg vials
Note: You will need to prepare a sterile and non-sterile field before
beginning product preparation.
Total preparation time: Allow at least 15 minutes for preparation
and an additional 15 minutes for protein to bind to collagen sponge.
(4) ACS 1" ∞ 2"
(2.54cm ∞ 5.08cm)
5.6cc graft volume
IN NON-STERILE FIELD
3.2mL
1
2
Observing proper sterile
technique, open the outer ACS
package and place the inner
package containing the four 1" ∞ 2"
collagen sponges in the sterile
field. Open and place two of the
four 5mL syringes/needles into
the sterile field.
3.2mL
3
Using one of the two
remaining 5mL syringes/
needles, withdraw 3.2mL of
sterile water for injection.
4
Reconstitute one vial of the
rhBMP-2 with 3.2mL of
sterile water.
Gently swirl (do not shake)
the rhBMP‑2 vial to ensure
adequate mixing. Using a
second 5mL syringe/needle,
repeat steps 2 and 3 with
the remaining vial of sterile
water and vial of rhBMP-2.
IN STERILE FIELD
1.4mL on
1st ACS
5
7
6
Open the inner ACS package
leaving all collagen sponges in
the plastic tray.
In the sterile field use the 5mL syringe/
needle to withdraw 1.4mL of reconstituted rhBMP-2 from the vial held by
the person in the non‑sterile field.
9
10
In the sterile field use the second
5mL syringe/needle to withdraw
1.4mL of reconstituted rhBMP-2 from
the second vial held by the person in
the non-sterile field.
!
Uniformly distribute 1.4mL of
reconstituted rhBMP-2 on the
third 1" ∞ 2" collagen sponge.
Allow wetted collagen sponges to stand for a minimum of 15 minutes.
Use within 2 hours. DO NOT use irrigation or suction near implanted device.
Note: During handling avoid excessive squeezing of the wetted sponge.
8
Uniformly distribute 1.4mL of
reconstituted rhBMP‑2 on one of
the 1" ∞ 2" collagen sponges.
1.4mL on
3rd ACS
1.4mL on
2nd ACS
1.4mL on
4th ACS
11
Using the second 5mL syringe/
needle, repeat steps 9 and 10 for
the fourth 1" ∞ 2" collagen sponge.
Using the same 5mL syringe/
needle, repeat steps 6 and 7
for the second 1" ∞ 2" collagen
sponge.
17
18
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Preparation of INFUSE ® Bone Graft Component (continued)
7510600 Large Kit (8.0cc)
(1) 10mL vial
(1) 12mg vial
Note: You will need to prepare a sterile and non-sterile field before
beginning product preparation.
Total preparation time: Allow at least 15 minutes for preparation
and an additional 15 minutes for protein to bind to collagen sponge.
(6) ACS 1" ∞ 2"
(2.54cm ∞ 5.08cm)
8.0cc graft volume
IN NON-STERILE FIELD
8.4mL
1
2
Observing proper sterile technique,
open the outer ACS package and
place the inner package containing
the six 1" ∞ 2" collagen sponges in
the sterile field. Open and place
one of the two 10mL syringes/
needles into the sterile field.
Using the other 10mL syringe/
needle, withdraw 8.4mL of
sterile water for injection.
8.4mL
3
4
Reconstitute the rhBMP‑2 with
8.4mL of sterile water.
Gently swirl (do not shake)
the rhBMP‑2 vial to ensure
adequate mixing.
IN STERILE FIELD
4.0mL on
1st three ACS
5
6
Open the inner ACS package
leaving all collagen sponges in
the plastic tray.
!
In the sterile field use
the 10mL syringe/needle
to withdraw 4.0mL of
reconstituted rhBMP‑2 from
the vial held by the person in
the non‑sterile field.
Allow wetted collagen sponges to stand for a minimum of 15 minutes.
Use within 2 hours. DO NOT use irrigation or suction near implanted device.
Note: During handling avoid excessive squeezing of the wetted sponge.
7
Uniformly distribute 4.0mL
of reconstituted rhBMP‑2 on
three of the 1" ∞ 2" collagen
sponges.
4.0mL on 2nd
three ACS
8
Using the same 10mL
syringe/needle, repeat steps
6 and 7 for the remaining
1" ∞ 2" collagen sponges.
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Preparation of INFUSE ® Bone Graft Component (continued)
7510800 Large II Kit (8.0cc)
(1) 10mL vial
(1) 12mg vial
Note: You will need to prepare a sterile and non-sterile field before
beginning product preparation.
Total preparation time: Allow at least 15 minutes for preparation
and an additional 15 minutes for protein to bind to collagen sponge.
(1) ACS 3" ∞ 4"
(7.62cm ∞ 10.16cm)
8.0cc graft volume
IN NON-STERILE FIELD
8.4mL
1
2
Observing proper sterile technique,
open the outer ACS package and
place the inner package containing
the 3" ∞ 4" collagen sponge in the
sterile field. Open and place one of
the two 10mL syringes/needles into
the sterile field.
Using the other 10mL syringe/
needle, withdraw 8.4mL of
sterile water for injection.
8.4mL
3
4
Reconstitute the rhBMP‑2
with 8.4mL of sterile water.
Gently swirl (do not shake)
the rhBMP‑2 vial to ensure
adequate mixing.
IN STERILE FIELD
4.0mL on 1st
half ACS
5
6
Open the inner ACS package. Using
sterile scissors, cut the 3" ∞ 4"
collagen sponge into two 1 1/2" ∞ 4"
strips. Return the cut collagen
sponges to the plastic tray.
!
In the sterile field use the 10mL
syringe/needle to withdraw 4.0mL
of reconstituted rhBMP-2 from the
vial held by the person in the
non‑sterile field.
Allow wetted collagen sponges to stand for a minimum of 15 minutes.
Use within 2 hours. DO NOT use irrigation or suction near implanted device.
Note: During handling avoid excessive squeezing of the wetted sponge.
7
Uniformly distribute 4.0mL
of reconstituted rhBMP‑2 on
one of the 1 1/2" ∞ 4" collagen
sponges.
4.0mL on 2nd
half ACS
8
Using the 10mL syringe/
needle, repeat steps 6 and 7
for the remaining 1 1/2" ∞ 4"
collagen sponge.
19
20
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Device Implantation
Using forceps, roll the wetted collagen sponges and place inside the LT-Cage® Device components (Figure 16
and 16A).
LT-Cage® Device components have specific Implant Holders located in the size-specific tray. Select the
correct Implant Holder for the device size. The distal end of the Implant Holder consists of two contact fingers.
Hold the two contact fingers and pass the Implant Holder through the Implant Driver Sleeve. Thread the
Holder to the Driver Sleeve until finger tight. Connect a T-Handle to the proximal end of the Driver Assembly
(Figure 17).
After preparing the LT-Cage® Device component for implantation, fit the two contact fingers onto the two
flat sides of the device (Figure 17A). While holding the device in place, turn the Implant Driver Sleeve clockwise
to tighten the contact fingers around the device. The LT‑Cage® Device component is securely in place when
there is no space between the tip of the Implant Holder and the Implant Driver Shaft.
Tip: Use the Implant Driver Wrench to fully tighten
the LT-CAGE Device to the Implant Driver.
®
Figure 16
Figure 16A
Figure 17A
Figure 17
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Device Implantation (continued)
The LT-CAGE® Device component is passed through the Outer Sleeve and inserted into
the cylindrical, reamed feature (Figure 18). The proximal end of the device is flush with
the anterior apex of the vertebral body when the first concentric ring on the Implant
Driver is aligned with the top of the Outer Sleeve.
Each subsequent ring indicates 3mm of device countersink. Advance device until the
proper countersink level is reached (Figure 18A). Device insertion must be completed
with the T-Handle parallel to the disc space. AP and lateral fluoroscopic checks are
recommended to confirm device positioning (Figure 18B).
Tip: The final position of the devices should
be slightly countersunk (2mm–5mm) from
the anterior cortex of the vertebral body.
Figure 18
Figure 18A
The Implant Driver is disengaged from the LT-CAGE® Device
component by unscrewing the Outer Sleeve of the Implant
Driver in a counterclockwise fashion. If necessary, the Implant
Driver Wrench may be used at the collar of the Outer Sleeve to
provide additional leverage in loosening the Implant Driver.
The second LT-CAGE® Device component is placed at the same
depth as the first LT-CAGE® Device component. To ensure the
placement is correct, confirm with a lateral C-arm view.
Figure 18B
21
22
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Device Implantation (continued)
In the final position, the INFUSE® Bone Graft/LT-CAGE® Device component should be slightly countersunk
(2mm–5mm) from the anterior surface and within the lateral margins of the vertebral bodies.
If necessary, an Implant Adjuster can be inserted into the proximal end of the device for alignment corrections.
The T-handle should be placed parallel with the disc space when the final device depth is achieved.
In order to countersink the device, adequate reaming depth must have been achieved. For example, if a
23mm length device is being inserted, the reaming depth must be greater than 23mm to allow the device to
be countersunk. Trying to countersink in the setting of inadequate reaming may result in stripping and the
potential loss or damage to the device-host interface.
A lateral fluoroscopic image may be taken to ensure proper final placement.
Tip: Re-attach the Implant Driver if the final
depth of the device needs to be adjusted.
Figure 19
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Single Barrel Technique Steps
1. Use the Centering Pin to identify and mark midline.
2.Use the appropriate sized Template to determine the width of the block discectomy. Complete the
block discectomy as described in this technique, step 1.
3.Insert the Single Barrel Distractor in Side A. Use the Single Barrel Distractor Driver Cap to seat the
Distractor Tip in place.
4.Guide the Single Barrel Outer Sleeve over the Distractor.
5.Placing the Impactor Cap over the Outer Sleeve, seat the Outer Sleeve so that it engages the
disc space. Use the Single Barrel Driver Cap to fully seat the Outer Sleeve. Remove the Single
Barrel Distractor.
6.Fit the Reamer with the Depth Stop and ream to the desired depth.
7.Remove the Reamer, insert the Reaming Plug within the Outer Sleeve and seat in the disc space.
Remove the Reaming Plug Shaft and the Outer Sleeve.
8.Repeat steps 3 through 7 to Side B.
9.Utilizing the assembled Inserter, attach the LT-CAGE® Device component and insert into Side B.
10.After implanting the first LT-CAGE® Device component into Side B, remove the Reaming Plug from
Side A and seat the Outer Sleeve to aid in vessel protection.
11.Insert the second LT-CAGE® Device component into Side A using the technique described in step 9.
23
24
Open Surgical Technique
INFUSE® BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE
Lumbar Tapered Instruments
GENERAL INSTRUMENTS
890-501
Instrument Remover, Large
890-502
Quick Disconnect T-handle
901-405
Starter Distractor Driver
901-406
6mm Starter Distractor
901-408
8mm Starter Distractor
901-410
10mm Starter Distractor
901-412
12mm Starter Distractor
901-450
Centering Pin/Template Shaft
901-451
Centering Pin/Template Shaft
901-456
Driver Cap
902-112
Adjustable Depth Stop
902-126
Reamer Clean Out Tool
9116882
I.V.D. Rongeur, 7mm ∞ 12mm
8950001
Double Distractor Driver Cap
8950003 Implant Driver Wrench
8950012
Adjustable Tapered Cage Holder
8951401
Discectomy Template, 14mm
8951601
Discectomy Template, 16mm
8951801
Discectomy Template, 18mm
14mm INSTRUMENTS
8951402
Standard Distractor, 14mm ∞ 10mm
8951403
C-Styled Distractor, 14mm ∞ 10mm
8951404
Double Barrel Outer Sleeve, 14mm
8951405
14mm Implant Hollow Reamer
8951407
14mm Implant Reamer Plug
8951408
14mm Implant Driver Sleeve
8951409
Implant Holder, 14mm ∞ 20mm
8951410
Implant Holder, 14mm ∞ 23mm
8951416
14mm Implant Adjuster
16mm INSTRUMENTS
8951602
Standard Distractor, 16mm ∞ 12mm
8951603
C-Styled Distractor, 16mm ∞ 12mm
8951604
Double Barrel Outer Sleeve, 16mm
8951605
16mm Implant Hollow Reamer
8951607
16mm Implant Reamer Plug
8951608
16mm Implant Driver Sleeve
8951609
Implant Holder, 16mm ∞ 20mm
8951610
Implant Holder, 16mm ∞ 23mm
8951611
Implant Holder, 16mm ∞ 26mm
8951616
16mm Implant Adjuster
8mm INSTRUMENTS
8951802
Standard Distractor, 18mm ∞ 14mm
8951803
C-Styled Distractor, 18mm ∞ 14mm
8951804
Double Barrel Outer Sleeve, 18mm
8951805
18mm Implant Hollow Reamer
8951807
18mm Implant Reamer Plug
8951808
18mm Implant Driver Sleeve
8951810
Implant Holder, 18mm ∞ 23mm
8951811
Implant Holder, 18mm ∞ 26mm
8951816
18mm Implant Adjuster
SINGLE BARREL INSTRUMENTS
8950005 Single Outer Sleeve Driver Cap
8950013
Single Barrel Reamer Plug Shaft
8951413
Single Barrel Reamer Plug, 14mm
8951414
Single Distractor, 14mm ∞ 10mm
8951415
Single Barrel Outer Sleeve, 14mm
8951613
Single Barrel Reamer Plug, 16mm
8951614
Single Distractor, 16mm ∞ 12mm
8951615
Single Barrel Outer Sleeve, 16mm
8951813
Single Barrel Reamer Plug, 18mm
8951814
Single Distractor, 18mm ∞ 14mm
8951815
Single Barrel Outer Sleeve, 18mm
INFUSE ® Bone Graft Components
7510050 7510100 INFUSE® BONE GRAFT XX SMALL KIT
One (1) Vial of Sterile rhBMP-2 (1.05mg)
One (1) Package of 1 Absorbable Collagen Sponge
(ACS) ½" ∞ 2" (1.25cm ∞ 5cm)
One (1) Vial of Sterile Water for Injection (5mL)
Two (2) Sterile 3mL Syringes with 20 G 1½" Needle
INFUSE® BONE GRAFT X SMALL KIT
Two (2) Vials of Sterile rhBMP-2 (1.05mg)
One (1) Package of 1 Absorbable Collagen Sponge
(ACS) 1" ∞ 2" (2.5cm ∞ 5cm)
Two (2) Vials of Sterile Water for Injection (5mL)
Four (4) Sterile 3mL Syringes with 20 G 1½" Needle
7510200INFUSE® BONE GRAFT SMALL KIT
One (1) Vial of Sterile rhBMP-2 (4.2mg)
One (1) Package of 2 Sterile Absorbable Collagen Sponges
(ACS) 1" ∞ 2" (2.5cm ∞ 5cm)
One (1) Vial of Sterile Water for Injection (5mL)
Two (2) Sterile 5mL Syringes with 20G 11/2" Needle
7510400INFUSE® BONE GRAFT MEDIUM KIT
Two (2) Vials of Sterile rhBMP-2 (4.2mg)
One (1) Package of 4 Sterile Absorbable Collagen Sponges
(ACS) 1" ∞ 2" (2.5cm ∞ 5cm)
Two (2) Vials of Sterile Water for Injection (5mL)
Four (4) Sterile 5mL Syringes with 20G 11/2" Needle
7510600INFUSE® BONE GRAFT LARGE KIT
One (1) Vial of Sterile rhBMP-2 (12mg)
One (1) Package of 6 Sterile Absorbable Collagen Sponges
(ACS) 1" ∞ 2" (2.5cm ∞ 5cm)
One (1) Vial of Sterile Water for Injection (10mL)
Two (2) Sterile 10mL Syringes with 20G 11/2" Needle
7510800INFUSE® BONE GRAFT LARGE II KIT
One (1) Vial of Sterile rhBMP-2 (12 mg)
One (1) Package of 1 Sterile Absorbable Collagen Sponge
(ACS) 1" ∞ 2" (2.5cm ∞ 5cm)
One (1) Vial of Sterile Water for Injection (10mL)
Two (2) Sterile 10mL Syringes with 20G 11/2" Needle
INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device
INFUSE® Bone Graft/INTER FIX™ Threaded Fusion Device
INFUSE® Bone Graft/INTER FIX™ RP Threaded Fusion Device – Reduced Profile
Important Medical Information
CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician with
appropriate training.
The following contains important medical information on the use of INFUSE® Bone Graft with a
variety of Medtronic metallic interbody fusion cages. These interbody fusion devices include the
LT-CAGE® Lumbar Tapered Fusion Device, the INTER FIX™ Threaded Fusion Device, and the INTER
FIX™ RP Threaded Fusion Device. Hereafter in this insert, these cages will be referred to collectively
as Medtronic Titanium Threaded Interbody Fusion Device.
DESCRIPTION
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device consists of
two components containing three parts– a metallic spinal fusion cage, a recombinant human
bone morphogenetic protein and a carrier/scaffold for the bone morphogenetic protein and
resulting bone. The INFUSE® Bone Graft component is inserted into the Medtronic Titanium
Threaded Interbody Fusion Device component to form the complete INFUSE® Bone Graft/
Medtronic Titanium Threaded Interbody Fusion Device. These components must be used as
a system for the prescribed indication described below. The bone morphogenetic protein
solution component must not be used without the carrier/scaffold component or with a carrier/scaffold component different from the one described in this document. The INFUSE®
Bone Graft component must not be used without the Medtronic Titanium Threaded Interbody
Fusion Device component.
Various sizes of the INFUSE® Bone Graft kit are available based on the internal volume of the
Medtronic Titanium Threaded Interbody Fusion Device component that is selected. The tables below
list the appropriate INFUSE® Bone Graft kit for the corresponding Medtronic Titanium Threaded
Interbody Fusion Device component size:
INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations
LT-CAGE® Lumbar Tapered
Appropriate INFUSE® Bone Graft Kit
Fusion Device
Reconstituted
Size (lead diameter,
rhBMP-2/ACS graft
volume
Part #
mm ∞ length, mm)
Part #
Kit name (size in cc)
8941420
14 ∞ 20
7510200
Small (2.8)
2.8ml
8941423
14 ∞ 23
7510200
Small (2.8)
2.8ml
8941620
16 ∞ 20
7510200
Small (2.8)
2.8ml
8941623
16 ∞ 23
7510400
Medium (5.6)
5.6ml
8941626
16 ∞ 26
7510400
Medium (5.6)
5.6ml
8941823
18 ∞ 23
7510400
Medium (5.6)
5.6ml
8941826
18 ∞ 26
7510600
Large Pre-Cut (8.0)
8.0ml
8941826
18 ∞ 26
7510800
Large II ( 8.0)
8.0ml
INFUSE® Bone Graft/INTER FIX™ Threaded Fusion Device Combinations
(Dual INTER FIX™ Devices)
INTER FIX™ Threaded
Fusion Device
Appropriate INFUSE® Bone Graft Kit
Part #
Size (diameter,
mm ∞ length, mm)
Part #
Kit name
(size in cc)
Reconstituted
rhBMP-2/ACS
graft volume
890120
12 ∞ 20
7510200
Small (2.8)
2.8ml
890125
12 ∞ 25
7510200
Small (2.8)
2.8ml
890140
14 ∞ 20
7510200
Small (2.8)
2.8ml
890143
14 ∞ 23
7510200
Small (2.8)
2.8ml
890146
14 ∞ 26
7510200
Small (2.8)
2.8ml
890149
14 ∞ 29
7510200
Small (2.8)
2.8ml
890160
16 ∞ 20
7510200
Small (2.8)
2.8ml
890163
16 ∞ 23
7510200
Small (2.8)
2.8ml
890166
16 ∞ 26
7510400
Medium (5.6)
5.6ml
890169
16 ∞ 29
7510400
Medium (5.6)
5.6ml
890180
18 ∞ 20
7510400
Medium (5.6)
5.6ml
890183
18 ∞ 23
7510400
Medium (5.6)
5.6ml
INTER FIX™ Threaded Fusion Device
The INTER FIX™ device consists of a hollow, perforated, cylinder with parallel sides and an endcap.
The cage is available in diameters ranging from 12mm to 24mm and in lengths ranging from 20mm
to 29mm. The endcaps of the INTER FIX™ cages are sized according to the diameter of the cylinders
and are applied to the open end of the cylinders after they are filled with INFUSE® Bone Graft.
890186
18 ∞ 26
7510400
Medium (5.6)
5.6ml
890189
18 ∞ 29
7510400
Medium (5.6)
5.6ml
890200
20 ∞ 20
7510400
Medium (5.6)
5.6ml
890203
20 ∞ 23
7510400
Medium (5.6)
5.6ml
The INTER FIX™ Threaded Fusion Device implants are made from implant grade titanium alloy
(Ti-6Al-4V) described by such standards as ASTM F136 or its ISO equivalent.
890206
20 ∞ 26
7510600 or 7510800
Large (8.0)*
8.0ml
890209
20 ∞ 29
7510600 or 7510800
Large (8.0)*
8.0ml
890220
7510600 or 7510800
Large (8.0)*
8.0ml
The INTER FIX™ Threaded Fusion Device component is sold separately from the INFUSE®
Bone Graft component, however, these two components must be used together. The package
labeling for the INTER FIX™ Threaded Fusion Device contains complete product information
for this component.
22 ∞ 20
890223
22 ∞ 23
7510600 or 7510800
Large (8.0)*
8.0ml
890240
24 ∞ 20
7510600 or 7510800
Large (8.0)*
8.0ml
Medtronic Titanium Threaded Interbody Fusion Device component
LT-CAGE® Lumbar Tapered Fusion Device
The LT-CAGE® device consists of a hollow, perforated, machined cylinder with opposing flat sides. The
cage has a tapered design with an angle of 8.8° and is available in diameters ranging from 14mm to
18mm at the narrow end of the taper, 17mm to 22 mm at the wide end of the taper and in lengths ranging from 20mm to 26mm. There are two holes on each of the two flat sides. On each of the two rounded
aspects, there is a single rounded slot. The implants have a helical screw thread on the outer surface. One
end of the device is closed. The other end is open to be filled with the INFUSE® Bone Graft component.
LT-CAGE®
The
implants are made from implant grade titanium alloy (Ti-6Al-4V) described by such
standards as ASTM F136 or its ISO equivalent.
LT-CAGE®
The
Lumbar Tapered Fusion Device component is sold separately from the
Bone
Graft component, however, these two components must be used together. The package labeling for the
®
LT-CAGE Lumbar Tapered Fusion Device contains complete product information for this component.
INFUSE®
INTER FIX™ RP Threaded Fusion Device
The INTER FIX™ RP device consists of a hollow, perforated, cylinder with a single, large, outer radiused
groove along the entire longitudinal axis that extends into the inside diameter of the device. Both ends of
the INTER FIX™ RP implant are closed. The cage is available in diameters ranging from 12mm to 24mm
and in lengths ranging from 20mm to 29mm.
The INTER FIX™ RP Threaded Fusion Device implants are made from implant grade titanium alloy
(Ti-6Al-4V) described by such standards as ASTM F136 or its ISO equivalent.
FIX™
The INTER
RP Threaded Fusion Device component is sold separately from the
Bone Graft component, however, these two components must be used together. The package
labeling for the INTER FIX™ RP Threaded Fusion Device contains complete product information
for this component.
INFUSE®
NOTE: The INTER FIX™ Threaded Fusion Device and the INTER FIX™ RP Threaded Fusion
Device may be used together to treat a spinal level. LT-CAGE® Lumbar Tapered Fusion Device
implants are not to be used in conjunction with either the INTER FIX™ OR INTER FIX™ RP
implants to treat a spinal level.
INFUSE® Bone Graft component
INFUSE® Bone Graft consists of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2,
known as dibotermin alfa) placed on an absorbable collagen sponge (ACS). The INFUSE® Bone
Graft component induces new bone tissue at the site of implantation. Based on data from nonclinical studies, the bone formation process develops from the outside of the implant towards the
center until the entire INFUSE® Bone Graft component is replaced by trabecular bone.
INFUSE®
rhBMP-2 is the active agent in the
Bone Graft component. rhBMP-2 is a disulfidelinked dimeric protein molecule with two major subunit species of 114 and 131 amino acids.
Each subunit is glycosylated at one site with high-mannose-type glycans. rhBMP-2 is produced
by a genetically engineered Chinese hamster ovary cell line.
rhBMP-2 and excipients are lyophilized. Upon reconstitution, each milliliter of rhBMP-2 solution contains: 1.5 mg of rhBMP-2; 5.0 mg sucrose, NF; 25 mg glycine, USP; 3.7 mg L-glutamic
acid, FCC; 0.1 mg sodium chloride, USP; 0.1 mg polysorbate 80, NF; and 1.0 mL of sterile water. The reconstituted rhBMP-2 solution has a pH of 4.5, and is clear, colorless and essentially
free from plainly visible particulate matter.
The ACS is a soft, white, pliable, absorbent implantable matrix for rhBMP-2. ACS is made from
bovine Type I collagen obtained from the deep flexor (Achilles) tendon. The ACS acts as a carrier for
the rhBMP-2 and acts as a scaffold for new bone formation.
* May be either the Large (Pre-Cut) or Large II Kit
INFUSE® Bone Graft/INTER FIX™ and INTER FIX™ RP Threaded Fusion Device Combinations
(INTER FIX™ RP Device with INTER FIX™ Device )
INTER FIX™ and INTER FIX™ RP
Threaded Fusion Devices
Appropriate INFUSE® Bone Graft Kit
Reconstituted
Part # of
Size
(diameter,
™
rhBMP-2/ACS
INTER FIX
Kit name
graft volume
Devices**
mm ∞ length, mm)
Part #
(size in cc)
890120
12 ∞ 20
7510200
Small (2.8)
2.8ml
890125
12 ∞ 25
7510200
Small (2.8)
2.8ml
890140
14 ∞ 20
7510200
Small (2.8)
2.8ml
890143
14 ∞ 23
7510200
Small (2.8)
2.8ml
890146
14 ∞ 26
7510200
Small (2.8)
2.8ml
890149
14 ∞ 29
7510200
Small (2.8)
2.8ml
890160
16 ∞ 20
7510200
Small (2.8)
2.8ml
890163
16 ∞ 23
7510200
Small (2.8)
2.8ml
890166
16 ∞ 26
7510400
Medium (5.6)
5.6ml
890169
16 ∞ 29
7510400
Medium (5.6)
5.6ml
890180
18 ∞ 20
7510400
Medium (5.6)
5.6ml
890183
18 ∞ 23
7510400
Medium (5.6)
5.6ml
890186
18 ∞ 26
7510400
Medium (5.6)
5.6ml
890189
18 ∞ 29
7510400
Medium (5.6)
5.6ml
890200
20 ∞ 20
7510400
Medium (5.6)
5.6ml
890203
20 ∞ 23
7510400
Medium (5.6)
5.6ml
890206
20 ∞ 26
7510600 or 7510800
Large (8.0)*
8.0ml
890209
20 ∞ 29
7510600 or 7510800
Large (8.0)*
8.0ml
890220
22 ∞ 20
7510600 or 7510800
Large (8.0)*
8.0ml
890223
22 ∞ 23
7510600 or 7510800
Large (8.0)*
8.0ml
890226
22 ∞ 26
7510600 or 7510800
Large (8.0)*
8.0ml
890229
22 ∞ 29
7510600 or 7510800
Large (8.0)*
8.0ml
890240
24 ∞ 20
7510600 or 7510800
Large (8.0)*
8.0ml
890243
24 ∞ 23
7510600 or 7510800
Large (8.0)*
8.0ml
* May be either the Large (Pre-Cut) or Large II Kit
** The INTER FIX™ Threaded Fusion Device should be used with the corresponding size of the
INTER FIX™ RP Threaded Fusion Device
WARNINGS
INFUSE® Bone Graft/INTER FIX™ RP Threaded Fusion Device Combinations
(Dual INTER FIX™ RP Devices)
INTER FIX™ RP
Threaded Fusion Device
Appropriate INFUSE® Bone Graft Kit
Part #
Size (diameter,
mm ∞ length, mm)
Part #
Kit name
(size in cc)
Reconstituted
rhBMP-2/ACS
graft volume
9011221
12 ∞ 20
7510200
Small (2.8)
2.8ml
9011225
12 ∞ 25
7510200
Small (2.8)
2.8ml
9011420
14 ∞ 20
7510200
Small (2.8)
2.8ml
9011423
14 ∞ 23
7510200
Small (2.8)
2.8ml
9011426
14 ∞ 26
7510200
Small (2.8)
2.8ml
9011429
14 ∞ 29
7510200
Small (2.8)
2.8ml
9011620
16 ∞ 20
7510200
Small (2.8)
2.8ml
9011623
16 ∞ 23
7510200
Small (2.8)
2.8ml
9011626
16 ∞ 26
7510400
Medium (5.6)
5.6ml
9011629
16 ∞ 29
7510400
Medium (5.6)
5.6ml
9011820
18 ∞ 20
7510400
Medium (5.6)
5.6ml
9011823
18 ∞ 23
7510400
Medium (5.6)
5.6ml
9011826
18 ∞ 26
7510400
Medium (5.6)
5.6ml
9011829
18 ∞ 29
7510400
Medium (5.6)
5.6ml
9012020
20 ∞ 20
7510400
Medium (5.6)
5.6ml
9012023
20 ∞ 23
7510400
Medium (5.6)
5.6ml
9012026
20 ∞ 26
7510400
Medium (5.6)
5.6ml
9012029
20 ∞ 29
7510400
Medium (5.6)
5.6ml
9012220
22 ∞ 20
7510400
Medium (5.6)
5.6ml
9012223
22 ∞ 23
7510400
Medium (5.6)
5.6ml
9012226
22 ∞ 26
7510600 or 7510800
Large (8.0)*
8.0ml
9012229
22 ∞ 29
7510600 or 7510800
Large (8.0)*
8.0ml
9012420
24 ∞ 20
7510600 or 7510800
Large (8.0)*
8.0ml
9012423
24 ∞ 23
7510600 or 7510800
Large (8.0)*
8.0ml
• In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are
capable of crossing the placenta. Reduced ossification of the frontal and parietal bones of
the skull was noted infrequently (<3%) in fetuses of rabbit dams immunized to rhBMP-2;
however, there was no effect noted in limb bud development. There are no adequate
and well-controlled studies in human pregnant women. Women of child bearing potential
should be warned by their surgeon of potential risk to a fetus and informed of other possible orthopedic treatments.
• Women of childbearing potential should be advised that antibody formation to rhBMP-2
or its influence on fetal development has not been completely assessed. In the clinical trial supporting the safety and effectiveness of the INFUSE® Bone Graft/LT-CAGE®
Lumbar Tapered Fusion Device, 2/277 (0.7%) patients treated with INFUSE® Bone Graft
component and 1/127 (0.8%) patients treated with autograft bone developed antibodies to rhBMP-2. The effect of maternal antibodies to rhBMP-2, as might be present
for several months following device implantation, on the unborn fetus is unknown.
Additionally, it is unknown whether fetal expression of BMP-2 could re-expose mothers
who were previously antibody positive. Theoretically, re-exposure may elicit a more
powerful immune response to BMP-2 with possible adverse consequences for the fetus. However, pregnancy did not lead to an increase in antibodies in the rabbit study.
Studies in genetically altered mice indicate that BMP-2 is critical to fetal development
and that a lack of BMP-2 activity may cause neonatal death or birth defects. It is not
known if anti-BMP-2 antibodies may affect fetal development or the extent to which
these antibodies may reduce BMP-2 activity.
• INFUSE® Bone Graft should not be used immediately prior to or during pregnancy.
Women of childbearing potential should be advised not to become pregnant for one
year following treatment with the INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device.
• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device in nursing mothers has not been established. It is not known if BMP-2
is excreted in human milk.
•
The safety and effectiveness of the use of the INFUSE® Bone Graft component with other spinal
implants, implanted at locations other than the lower lumbar spine, or used in surgical techniques other than anterior open (LT-CAGE®, INTER FIX™, INTER FIX™ RP devices) or anterior
laparoscopic (LT-CAGE® device) approaches have not been established.
* May be either the Large (Pre-Cut) or Large II Kit
– When degenerative disc disease was treated by a posterior lumbar interbody fusion procedure with cylindrical threaded cages (INTER FIX™ devices), posterior bone formation was
observed in some instances.
Each kit contains all the components necessary to prepare the INFUSE® Bone Graft component: the
rhBMP-2 which must be reconstituted, sterile water, absorbable collagen sponges, syringes with
needles, this package insert and instructions for preparation. The number of each item may vary
depending on the size of the kit.
– When anterior cervical spinal fusions were performed using the INFUSE® Bone Graft
component, some cases of edema have been reported within the first post-operative
week. In some of these cases, this swelling has been severe enough to produce airway
compromise, sometimes requiring emergency surgery.
In the event that part of one of these kits becomes unusable during surgery, additional XS and
XXS kits are available for replacement purposes The XS and XXS kits also provide amounts that
more closely match the volumes in certain smaller cages (see the XS and XXS package insert for
the kit and cage combinations). For instructions on using the XS and XXS kits, please refer to the
package insert for these products (7510050 and 7510100).
The rhBMP-2 is provided as a lyophilized powder in vials delivering either 4.2 mg or 12 mg of protein.
After appropriate reconstitution, both configurations result in the same formulation and concentration
(1.5 mg/mL) of rhBMP-2. The solution is then applied to the provided absorbable collagen sponge(s).
The INFUSE® Bone Graft component is prepared at the time of surgery and allowed a prescribed
amount of time (no less than 15 minutes) before placement inside of the Medtronic Titanium Threaded
Interbody Fusion Device components. The Instructions for Preparation contain complete details on
preparation of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device.
•
The implantation of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device using
an anterior laparoscopic surgical approach is associated with a higher incidence of retrograde
ejaculation when compared to implantation using an anterior open surgical approach.
•
Inappropriate use of the product, such as preparing it differently than prescribed, compressing
the rhBMP-2/ACS implant more than necessary, or overfilling the volume intended for new bone
formation, may change the concentration of the rhBMP-2, which may inhibit the ability of the
rhBMP-2/ACS to convert to bone and/or cause complications. Such use of the rhBMP-2/ACS
implant may result in radiographic evidence of resorption, fluid formation, and/or edema. These
findings may be asymptomatic or symptomatic.
•
While there are currently anecdotal and literature evidence to suggest that volume overfilling
and/or hyperconcentration of the rhBMP-2 solution may lead to fluid formation and/or edema,
animal models for scientifically evaluating these events do not presently exist. A sheep model
developed to test the hypothesis that volume overfilling and/or hyperconcentration of the
rhBMP-2 solution results in radiographic evidence of bone resorption has preliminarily been
evaluated and appears to be supportive of the hypothesized mechanism.
•
Placement of rhBMP-2/ACS can cause initial resorption of trabecular bone that may be transient.
•
Nerve compression associated with ectopic bone formation has been reported in patients undergoing
spine surgery with rhBMP-2/ACS. Surgical intervention may be required to address the symptoms.
No warranties, express or implied, are made. Implied warranties of merchantability and fitness for
a particular purpose or use are specifically excluded.
INDICATIONS
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is indicated for spinal
fusion procedures in skeletally mature patients with degenerative disc disease (DDD) at one level from
L2 – S1. DDD is defined as discogenic back pain with degeneration of the disc confirmed by patient
history and radiographic studies. These DDD patients may also have up to Grade I spondylolisthesis or
Grade 1retrolisthesis at the involved level. Patients receiving the INFUSE® Bone Graft/ Medtronic Titanium Threaded Interbody Fusion Device should have had at least six months of nonoperative treatment
prior to treatment with the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device.
The INFUSE® Bone Graft with the LT-CAGE® Lumbar Tapered Fusion Device is to be implanted via an
anterior open or an anterior laparoscopic approach. The INFUSE® Bone Graft with either the INTER FIX™
or the INTER FIX™ RP Threaded Fusion Device is to be implanted via an anterior open approach.
CONTRAINDICATIONS
• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is contraindicated for patients with a known hypersensitivity to recombinant human Bone Morphogenetic
Protein-2, bovine Type I collagen or to other components of the formulation.
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
used in the vicinity of a resected or extant tumor, in patients with any active malignancy or
patients undergoing treatment for a malignancy.
•
INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be used
in patients who are skeletally immature (<18 years of age or no radiographic evidence of epiphyseal closure).
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be used
in pregnant women. The potential effects of rhBMP-2 on the human fetus have not been evaluated.
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
implanted in patients with an active infection at the operative site or with an allergy to titanium
or titanium alloy.
PRECAUTIONS
General
• The safety and effectiveness of repeat applications of the INFUSE® Bone Graft component has
not been established.
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should only
be used by surgeons who are experienced in spinal fusion procedures and have undergone
adequate training with this device, for anterior laparoscopic and/or anterior open procedures.
•
Two Medtronic Titanium Threaded Interbody Fusion Device components should be implanted
side by side at the surgical level whenever possible.
•
The Medtronic Titanium Threaded Interbody Fusion Device components and instruments must
be sterilized prior to use according to the sterilization instructions provided in the package insert
for that component, unless supplied sterile and clearly labeled as such.
•
When using this device at spinal levels between L2 and L4, the potential impact of anatomical
structures, e.g., the aorta, on implant placement must be considered.
•
The formation of exuberant or ectopic bone growth at the upper lumbar levels (L2– L4) may
have a deleterious impact on certain neurovascular structures, e.g., the aorta and sympathetic
nerve chain.
•
The safety and effectiveness of the device at spinal levels L2– L4 or in patients with up to Grade
1 retrolisthesis has not been established.
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is intended for
single use only. Discard unused product and use a new device for subsequent applications.
•
Prior to use, inspect the packaging, vials and stoppers for visible damage. If damage is
visible, do not use the product. Retain the packaging and vials and contact a Medtronic
representative.
•
Do not use after the printed expiration date on the label.
Immunogenicity
• As with all therapeutic proteins, there is a potential for immune responses to be generated to the
INFUSE® Bone Graft component. The immune response to the INFUSE® Bone Graft components was
evaluated in 349 investigational patients and 183 control patients receiving lumbar interbody fusions.
Anti-rhBMP-2 antibodies: 2/349 (0.6%) patients receiving the INFUSE® Bone Graft component
developed antibodies vs. 1/183 (0.5%) in the control group.
Hepatic and Renal Impairment
• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device in patients with hepatic or renal impairment has not been established.
Pharmacokinetic studies of rhBMP-2 indicate that the renal and hepatic systems are involved
with its clearance.
Geriatrics
• Clinical studies of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device did not
include sufficient numbers of patients 65 years and older to determine whether they respond
differently from younger subjects.
Anti-bovine Type I collagen antibodies: 18.1% of patients receiving the INFUSE® Bone Graft component developed antibodies to bovine Type I collagen vs. 14.2% of control patients. No patients in
either group developed anti-human Type I collagen antibodies.
The presence of antibodies to rhBMP-2 was not associated with immune mediated adverse events
such as allergic reactions. The neutralizing capacity of antibodies to rhBMP-2 is not known.
•
Bone formation
• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with metabolic bone diseases.
•
While not specifically observed in the clinical study, the potential for ectopic, heterotopic or
undesirable exuberant bone formation exists.
Antibody Formation/Allergic Reactions
• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with autoimmune disease.
•
The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device has not been demonstrated in patients with immunosuppressive disease or suppressed immune systems resulting from radiation therapy, chemotherapy, steroid
therapy or other treatments.
The incidence of antibody detection is highly dependent on the sensitivity and specificity of the
assay. Additionally, the incidence of antibody detection may be influenced by several factors
including sample handling, concomitant medications and underlying disease. For these reasons,
comparison of the incidence of antibodies to the INFUSE® Bone Graft component with the incidence of antibodies to other products may be misleading.
ADVERSE EVENTS
The INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device was implanted in 288 investigational patients and compared to 139 control patients who received an LT-CAGE® Lumbar Tapered
Fusion Device filled with iliac crest autograft. The investigational patients were implanted with the
device via either an open anterior surgical approach or a laparoscopic anterior surgical approach.
The control patients were implanted only via the open anterior surgical approach.
Adverse event rates presented are based on the number of patients having at least one occurrence
for a particular adverse event divided by the total number of patients in that treatment group. Because no control subjects were evaluated at the 48 and 72 month timepoints, the reported events
at these timepoints are only from the investigational subjects.
ADVERSE EVENTS
(INFUSE® Bone Graft/LT-CAGE® Device data combined from all experience with the device)
Postoperative
(1 day <4 Weeks)
Surgery
6 Weeks
(≥4 Weeks <9 Weeks)
3 Months
(≥9 Weeks <5 Months)
6 Months
(≥5 Months <9 Months)
12 Months
(≥9 Months <19 Months)
24 Months
(≥19 Months <30 Months)
Inves.
Control
Inves.
Control
Inves.
Control
Inves.
Control
Inves.
Control
Inves.
Control
Inves.
Control
Anatomical/Technical
Difficulty
11
3
0
0
0
0
0
0
0
0
0
0
0
0
Back and/or Leg Pain
0
0
12
4
11
5
12
5
8
11
20
7
8
11
Cancer
0
0
0
0
0
0
0
1
1
0
1
0
1
0
Cardio/Vascular
1
0
6
5
5
2
1
3
1
1
4
2
1
1
Death
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Dural Injury
0
0
0
0
0
0
0
1
0
0
0
0
0
0
Gastrointestinal
1
0
40
22
2
0
5
1
7
5
10
3
7
5
Complication
Graft Site Related
0
0
0
8
0
0
0
0
0
0
0
0
0
0
Implant
Displacement/
Loosening
0
0
1
1
3
0
1
0
0
0
0
0
0
0
Infection
0
0
19
9
8
4
5
1
0
2
3
0
0
2
Malpositioned Implant
5
0
0
0
0
0
0
0
0
0
0
0
0
0
Neurological
0
0
8
5
7
3
5
2
6
8
13
4
6
8
Non-Union*
0
0
0
0
0
0
0
0
1
1
4
0
1
1
Non-Union**
0
0
0
1
0
1
2
0
1
1
4
6
1
1
Other
5
6
18
11
9
2
3
4
20
7
15
8
20
7
Other Pain
0
0
3
1
2
1
4
2
10
3
11
8
10
3
Respiratory
0
0
3
2
1
0
0
0
0
1
0
1
0
1
Retrograde Ejaculation
0
0
5
1
4
0
1
0
0
0
2
0
0
0
Spinal Event
0
0
1
2
1
0
6
2
9
2
10
8
9
2
Subsidence
0
0
3
2
2
0
1
0
0
0
0
0
0
0
Trauma
0
0
4
5
5
3
11
7
19
8
28
11
19
8
Urogenital
0
0
24
5
3
0
2
3
7
2
3
1
7
2
Vascular Intra-Op
15
5
0
0
0
0
0
0
0
0
0
0
0
0
Vertebral Fracture
0
0
1
0
0
0
0
0
0
0
0
0
0
0
Any Adverse Event
* Non-union adverse events that have not resulted in a second surgery.
** Non-union adverse events that have resulted in a second surgery.
1 Percent of 140 males.
2 Percent of 70 males.
# of Patients Reporting &
Total adverse events
48 Months
(≥30 Months <60 Months)
72 Months
(≥60 Months <84 Months)
Investigational
# (% of 288)
total events
Control
#(% of 139)
total events
Total #
(% of 134)
total events
Total #
(% of 140)
total events
11 (3.8)
11
70 (24.3)
78
2 (0.7)
2
17 (5.9)
20
0 (0.0)
0
0 (0.0)
0
56 (19.4)
72
0 (0.0)
0
3 (2.2)
3
36 (23.0)
32
1 (0.7)
1
12 (8.6)
14
1 (0.7)
1
1 (0.7)
1
27 (19.4)
32
8 (5.8)
8
0 (0.0)
0
22 (16.4)
23
4 (3.0)
4
7 (5.2)
7
2 (1.5)
2
0 (0.0)
0
14 (10.4)
17
0 (0.0)
0
0 (0.0)
0
18 (12.9)
21
1 (0.7)
1
4 (2.9)
4
0 (0.0)
0
0 (0.0)
0
6 (4.3)
8
0 (0.0)
0
5 (1.7)
5
1 (0.7)
1
0 (0.0)
0
0 (0.0)
0
36 (12.5)
40
5 (1.7)
5
39 (13.5)
45
6 (2.1)
6
10 (3.5)
10
64 (22.2)
81
31 (10.8)
36
5 (1.7)
5
11 (7.9)1
12
30 (10.4)
37
7 (2.4)
7
69 (24.0)
81
41 (14.2)
45
14 (4.9)
15
1 (0.3)
1
235 (81.6)
16 (11.5)
17
0 (0.0)
0
23 (16.5)
24
3 (2.2)
3
13 (9.4)
13
37 (26.6)
42
14 (10.1)
1
4 (2.9)
4
1 (1.4)2
1
17 (12.2)
18
2 (1.4)
2
34 (24.5)
39
13 (9.4)
14
5 (3.6)
5
0 (0.0)
0
121 (87.1)
4 (3.0)
4
0 (0.0)
0
12 (9.0)
12
0 (0.0)
0
0 (0.0)
0
22 (16.4)
29
14 (10.4)
19
1 (0.7)
1
0 (0.0)
0
9 (6.7)
9
0 (0.0)
0
21 (15.7)
23
2 (1.5)
2
1 (0.7)
1
0 (0.0)
0
84 (62.7)
3 (2.1)
3
0 (0.0)
0
5 (3.6)
5
0 (0.0)
0
0 (0.0)
0
17 (12.1)
18
12 (8.6)
13
0 (0.7)
1
0 (0.0)
0
8 (5.7)
8
0 (0.0)
0
20 (14.3)
22
3 (2.1)
3
0 (0.0)
0
0 (0.0)
0
64 (45.7)
The reported rates of several adverse events were high, but similar, in both the investigational
and control groups. These events included back and leg pain, neurological events, gastrointestinal
events, spinal events, cardiovascular events and infection.
Some of the reported adverse events required surgical interventions subsequent to the initial surgery. The number of subjects requiring a second surgical intervention was 10.4% (30/288) in the
investigational groups and 13.7% (19/139) in the control group. The majority of supplemental fixations were due to painful non-union.
Urogenital events occurred with greater frequency in the investigational groups (11.5%) compared
to the control group (7%). Retrograde ejaculation rates were greater in the investigational groups
(11 subjects) compared to the control group (1 subject) with the majority of events occurring in the
early postoperative period.
The incidence of adverse events that were considered device related, including implant displacement/loosening, implant malposition and subsidence were all greater in the investigational groups
compared to the control group. The rates of these events were low, however, and may be partially
attributed to a learning curve associated with the laparoscopic surgical approach. The rate of nonunion requiring secondary surgery in the investigational groups was comparable to that of the
control group. One death was reported - a control group subject with cardiovascular disease.
Potential Adverse Events
The following is a list of potential adverse events which may occur with spinal fusion surgery with
the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device. Some of these
adverse events may have been previously reported in the adverse events table or have been reported
to the manufacturer:
• Bone fracture.
• Bowel or bladder problems.
• Cessation of any potential growth of the operated portion of the spine. Loss of spinal mobility or
function.
• Change in mental status.
• Damage to blood vessels and cardiovascular system compromise.
• Damage to internal organs and connective tissue.
• Death.
• Development of respiratory problems.
• Disassembly, bending, breakage, loosening, and/or migration of components.
• Dural tears.
• Ectopic and/or exuberant bone formation.
• Fetal development complications.
• Foreign body (allergic) reaction.
• Gastrointestinal complications.
• Incisional complications.
• Infection.
• Insufflation complications.
• Neurological system compromise.
• Non-union (or pseudarthrosis), delayed union, mal-union.
• Postoperative change in spinal curvature, loss of correction, height, and/or reduction.
• Retrograde ejaculation.
• Scar formation.
• Tissue or nerve damage.
• Edema (swelling).
• Inflammation.
• Erythematous tissue.
• Allergic reaction.
• Itching.
• Anaphylactic reaction.
• Elevated erythrocyte sedimentation rate.
• Pain.
• Hematoma.
Note: Additional surgery may be necessary to correct some of these potential adverse events.
CLINICAL RESULTS
Clinical data to support the safety and effectiveness of the INFUSE® Bone Graft/ LT-CAGE® Lumbar Tapered Fusion Device were collected as part of a prospective, multi-center pivotal study that
consisted of randomized and non-randomized arms. The randomized arm contained two groups,
one investigational and one control. The control group was implanted with the LT-CAGE® Lumbar
Tapered Fusion Device filled with iliac crest autograft bone, while the investigational group was
implanted with the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device. In both cases,
the surgical approach was an open anterior approach. The non-randomized arm contained only
an investigational group, where subjects were implanted with the INFUSE® Bone Graft/LT-CAGE®
Lumbar Tapered Fusion Device through a laparoscopic anterior approach. The control group from
the randomized arm was used as the control for the non-randomized arm.
Neither the investigators nor the subjects were blinded to the treatment. Subject blinding was not
possible due to the second surgical site resulting from the need to collect the iliac crest grafts. The
potential for investigator bias in the clinical outcome parameters was reduced by having the subjects rate their outcome using objective self-assessments. The radiographic outcome parameters
were performed by independent radiologists who were blinded to treatment. These were the only
radiographic evaluations used for determining radiographic success.
The indication studied was degenerative disc disease (DDD) accompanied by back pain with or without leg pain at a single level between L4 and S1 confirmed by history and radiographic studies.
Clinical and radiographic effectiveness parameters
Patients were evaluated preoperatively (within 6 months of surgery), intraoperatively, and postoperatively at 6 weeks, 3, 6, 12 and 24 months and biennially thereafter until the last subject enrolled
in the study had been seen for their 24 month evaluation. Complications and adverse events, devicerelated or not, were evaluated over the course of the clinical trial. At each evaluation timepoint, the
primary and secondary clinical and radiographic outcome parameters were evaluated. Success was
determined from data collected during the initial 24 months of follow-up. Antibodies to rhBMP-2
and bovine Type I collagen were assessed preoperatively and at 3 months post-operatively. Antibodies to human Type I collagen were assessed if the antibody response to bovine Type I collagen
was positive.
Primary and secondary clinical and radiographic effectiveness outcome parameters were evaluated for all treated subjects at all follow-up evaluation timepoints identified above. The primary
clinical parameters assessed were of pain, function and neurological status. The secondary clinical outcome parameters assessed were general health status, back and leg pain, donor site pain
(control subjects only), patient satisfaction and patient global perceived effect of the treatment. The
primary radiographic outcome parameter consisted of evaluations of fusion, while the secondary
radiographic assessment was disc height.
Fusion was evaluated at 6, 12 and 24 months post-op using plain radiographs (AP, lateral and
flexion/extension films) and high resolution thin-slice CT scans (1mm slices with 1mm index on
axial sagittal and coronal reconstructions). Fusion was defined as the presence of bridging bone
connecting the inferior and superior vertebral bodies; a lack of motion on flexion/extension (≤ 3mm
of translation and < 5° of angulation); and no evidence of radiolucencies over more than 50% of
either implant. Fusion success was defined as the presence of all of these parameters plus the lack
of a second surgical intervention resulting from a non-union. All assessments were made from the
plain films except for the assessment of bridging bone, which was made using the CT scans only if
bridging bone could not be visualized on the plain film.
Pain and function were measured using the Oswestry Low Back Pain Disability Questionnaire. Success was defined as a 15 point improvement in the Oswestry score from the pre-op baseline score.
Neurological status consisted of measurements of four parameters – motor, sensory, reflexes,
and straight leg raise (SLR). Neurological status success was defined as maintenance or
improvement of the pre-op baseline score for each parameter. Overall neurological status
success required that each individual parameter be a success for that subject to be counted
as a success.
Patient demographics and accountability
A total of 143 open approach investigational and 136 control patients were enrolled in the randomized
arm of the study and received the device. A total of 134 subjects were enrolled in the non-randomized
arm of the study and received the device. For the majority of the demographic parameters, there were no
differences in pre-op demographics across the three populations.
Surgical results and hospitalization
Surgical and hospitalization information
Investigational Open
Surgical Approach
Control
Open Surgical
Approach
Investigational
Laparoscopic Surgical
Approach
mean operative time
(hrs)
1.6*
2.0
1.9
mean EBL (ml)
109.8*
153.1
146.1
hospitalization (days)
3.1
3.3
1.2*
*statistically different from control
Clinical and radiographic effectiveness evaluation
Individual subject success was defined as success in each of the primary clinical and radiographic
outcome parameters. Success for these parameters included:
1. the presence of radiographic fusion;
2. an improvement of at least 15 points from the baseline Oswestry score;
3. maintenance or improvement in neurological status;
4. the presence of no serious adverse event classified as implant-associated or implant/surgical
procedure-associated; and
5. no additional surgical procedure classified as “Failure.”
Study success was expressed as the number of individual subjects categorized as a success divided
by the total number of subjects evaluated. The table below describes the success rates for the
individual primary outcome parameters and overall success. All success rates were based on the
data from the 24 month follow-up evaluation and posterior probabilities of success were calculated
using Bayesian statistical methods.
Posterior Probabilities of Success at 24 Months
Investigational Open
Surgical Approach
Control Open
Surgical Approach
Investigational
Laparoscopic Surgical
Approach
Posterior Mean
(95% HPD
Credible Interval)
Posterior Mean
(95% HPD
Credible Interval)
Posterior Mean
(95% HPD
Credible Interval)
Fusion
92.8%
(88.5%, 96.9%)
88.1%
(82.6%, 99.3%)
93.0%
(87.9%, 97.5%)
Oswestry
71.0%
(63.4%, 78.7%)
70.9%
(63.1%, 79.1%)
83.0%
(75.6%, 90.5%)
Neurologic
81.0%
(74.5%, 87.9%)
81.7%
(74.9%, 88.7%)
89.0%
(83.1%, 94.8%)
Overall
success
57.1%
(49.2%, 65.7%)
56.7%
(48.3%, 65.0%)
68.0%
(59.3%, 76.5%)
Primary
outcome
variable
The probability (also called the posterior probability) that the 24 month overall success rate for
the investigational groups was equivalent to the 24 month success rate for the control group was
99.4% for the open surgical approach investigational group and almost 100% for the laparoscopic
surgical approach investigational group.
For a future patient receiving the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device via
the open anterior surgical approach, the chance (the predictive probability) of overall success at 24
months would be 57.1% for the open surgical approach. Given the results of the trial, there is a 95%
probability that the chance of success ranges from 49.2% to 65.7%. For a future patient receiving
the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device via the anterior laparoscopic
surgical approach, the chance of overall success at 24 months would be 68.0%. Given the results
of the trial, there is a 95% probability that the chance of success ranges from 59.3% to 76.5%. For
a future patient receiving the control treatment, the chance of overall success at 24 months would
be 56.7%. Given the results of the trial, there is a 95% probability that the chance of success ranges
from 48.3% to 65.0%.
Safety and immune response evaluation
The assessment of safety consisted of an evaluation of the reported adverse events, as well as an
evaluation of antibodies to rhBMP-2, bovine Type I collagen and human Type I collagen. The complete list of complications, adverse events and subsequent interventions is described in the Adverse
Events section above. The presence of antibodies was assessed at the pre-op and 3 month post-op
visits using ELISA. If there was a positive response to bovine Type I collagen, the serum was also
tested for antibodies to human Type I collagen. The screening ELISA cutpoint for positive antibody
responses was set to 5 times the standard deviation of sera from normal human donors. Subjects
were considered to have an elevated immune response if the preoperative test was negative (titer <
50) and postoperative test was positive (titer ≥ 50) or if the preoperative test was positive and the
postoperative test was positive with a three-fold higher titer than the preoperative test.
There were 3 subjects who had positive antibody responses to rhBMP-2 – 1 subject in each of the
study groups. The rates of positive antibody response to rhBMP-2 were 0.7% in the open surgical
approach investigational group and 0.8% in the laparoscopic surgical approach investigational and
open surgical approach control groups. While there is a theoretical possibility that antibodies to
rhBMP-2 could neutralize endogenous BMP-2, thereby interfering with subsequent bone healing,
this was not observed during the course of the study.
Sixty-six subjects were considered to have an authentic elevated antibody response to bovine Type
I collagen - 18 open surgical approach investigational subjects, 32 laparoscopic surgical approach
investigational subjects and 16 control subjects. No subjects had positive responses to human
Type I collagen.
An evaluation was performed on the impact of a positive antibody response on overall success and
fusion success. There was very little difference in overall and individual success when antibody
status was taken into consideration.
During the course of the study, 6 pregnancies were reported – one in the control group and five in
the investigational groups. Two of the four pregnancies that occurred in the laparoscopic approach
group resulted in first trimester miscarriages. The other three pregnancies in the investigational
groups resulted in live births with no reported complications. None of the pregnant subjects had
antibody responses to rhBMP-2 or Type I collagen (bovine or human), that were detectable to the
limits of the sensitivity of the assay.
Two cases of cancer were diagnosed during the course of the pivotal study – one in an investigational
group and one in the control group. An investigational subject was found to have pancreatic cancer
while a control subject was found to have breast cancer. No additional information is available on these
subjects, e.g., BMP-2 receptor expression.
Post-Approval Study
A total of 145 investigational subjects were evaluated out to 6 years (72 months) after the initial
surgery in a post-approval study. The patient population was obtained from participants in both the
open and laparoscopic arms of the IDE clinical trial. Control subjects from the IDE study were not
followed in the post-approval study. Based on criteria from the IDE study, information pertaining
to the safety and effectiveness of the product was obtained at four and six years post-implantation,
including adverse events, an independent radiographic assessment of fusion, and an assessment of
pain and function. The table below summarizes the clinical and radiographic data evaluated during
the post approval study, as well as the overall success rate at each timepoint.
Overall Success Rates – Post Approval Study
Variable
4-Year Evaluation
6-Year Evaluation
Overall Success
60.6% (77/127)
60.4% (84/139)
Oswestry Pain Improvement
81.5% (106/130)
79.0% (109/138)
Fusion
98.3% (117/119)
98.5% (128/130)
Neurological Status
(Maintenance or Improvement)
73.3% (96/131)
81.2% (112/138)
HOW SUPPLIED
INFUSE® Bone Graft component is supplied in various kit sizes containing all the components necessary to prepare this portion of the device, i.e., the collagen sponge(s), a vial with the lyophilized
growth factor, a vial with sterile water for reconstituting the growth factor, syringes and needles. The
Medtronic Titanium Threaded Interbody Fusion Device component is supplied in a variety of sizes
which must be properly selected based on a specific patient’s anatomy.
STORAGE CONDITIONS
Store the INFUSE® Bone Graft component at room temperature [15 – 30 degrees Centigrade (59
to 86° F)]. The Medtronic Titanium Threaded Interbody Fusion Device component should also be
stored at room temperature.
DOSAGE AND ADMINISTRATION
INFUSE® Bone Graft component is prepared immediately prior to use from a kit containing all
necessary components. Once prepared, the INFUSE® Bone Graft component contains rhBMP-2 at
a concentration of 1.5 mg/mL.
The size of the INFUSE® Bone Graft component kit and the volume of INFUSE® Bone Graft component to be implanted are determined by the internal volume of the Medtronic Titanium Threaded
Interbody Fusion Device components which are utilized. The patient’s anatomy will determine the
size of the Medtronic Titanium Threaded Interbody Fusion Device components to be used. Surgical technique manuals for the INFUSE® Bone Graft with the specific Medtronic Titanium Threaded
Interbody Fusion Devices referenced in this package insert are available and will provide more
information on templating to determine the appropriate size Medtronic Titanium Threaded Interbody
Fusion Device component.
Only store the components in this INFUSE® Bone Graft kit in the manner described on the package,
only mix the components in the manner described in the directions, only add the reconstituted
rhBMP-2 to the ACS carrier provided in the manner described, and only use in the quantity and
indication specified in the package insert. Any other storage, mixture, or administration may cause
unanticipated adverse events.
DIRECTIONS FOR USE
INFUSE® Bone Graft component is prepared at the time of surgery in the surgical suite by reconstituting the lyophilized rhBMP-2 with sterile water (See Instructions for Preparation), and then uniformly
applying the reconstituted rhBMP-2 solution to the ACS. The INFUSE® Bone Graft component is then
inserted into the Medtronic Titanium Threaded Interbody Fusion Device component. The complete device
is then implanted through an anterior surgical approach (See the Surgical Technique manual). If the
INFUSE® Bone Graft component is not used within two hours after reconstitution, it must be discarded.
The INFUSE® Bone Graft component must not be sterilized by the hospital. The Medtronic Titanium
Threaded Interbody Fusion Device component, if not supplied sterile, should be sterilized before
insertion of the INFUSE® Bone Graft component. Please refer to the specific Medtronic Titanium
Threaded Interbody Fusion Device package insert for information on packaging, cleaning/decontamination and sterilization of this component and its instruments.
PRODUCT COMPLAINTS
Any health care professional (e.g., customer or user of this system of products), who has any
complaints or who has experienced any dissatisfaction in the product quality, identity, durability,
reliability, safety, effectiveness and/or performance of this product, should notify the distributor
or Medtronic. Further, if any of the implanted INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device component(s) ever “malfunction,” (i.e., do not meet any of their performance specifications or otherwise do not perform as intended), or are suspected of doing so, the
distributor should be notified immediately. If any Medtronic product ever “malfunctions” and may
have caused or contributed to the death or serious injury of a patient, the distributor should be
notified immediately by telephone, fax or written correspondence. When filing a complaint, please
provide the component(s) name and number, lot number(s), your name and address, the nature of
the complaint and notification of whether a written report from the distributor is requested.
DEVICE RETRIEVAL EFFORTS
Should it be necessary to remove an INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device, please call Medtronic prior to the scheduled surgery to receive instructions regarding data collection, including histopathological, mechanical and adverse event information.
In USA
Customer Service Division
Telephone:
Medtronic Sofamor Danek USA, Inc.
1800 Pyramid Place
Memphis, Tennessee 38132
USA
Telefax:
800-933-2635
800-876-3133
or 901 396 3133
901 396 0356
Supplied by
Medtronic Sofamor Danek USA, Inc.
©2008 Medtronic Sofamor Danek, Inc. All rights reserved.
INFUSE® Bone Graft in combination with LT-CAGE®, INTER FIX™ or INTER FIX™ RP devices
incorporate technology developed by Gary K. Michelson, M.D.
INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device
INFUSE® Bone Graft/INTER FIX™ Threaded Fusion Device
INFUSE® Bone Graft/INTER FIX™ RP Threaded Fusion Device – Reduced Profile
X Small (1.4cc) & XX Small (0.7cc) INFUSE® Bone Graft Kits ONLY
Important Medical Information
CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician with
appropriate training.
The following contains important medical information on the use of INFUSE® Bone Graft with a
variety of Medtronic metallic interbody fusion cages. These interbody fusion devices include the
LT-CAGE® Lumbar Tapered Fusion Device, the INTER FIX™ Threaded Fusion Device, and the INTER
FIX™ RP Threaded Fusion Device. Hereafter in this insert, these cages will be referred to collectively
as Medtronic Titanium Threaded Interbody Fusion Device.
DESCRIPTION
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device consists of
two components containing three parts– a metallic spinal fusion cage, a recombinant human
bone morphogenetic protein and a carrier/scaffold for the bone morphogenetic protein and
resulting bone. The INFUSE® Bone Graft component is inserted into the Medtronic Titanium
Threaded Interbody Fusion Device component to form the complete INFUSE® Bone Graft/
Medtronic Titanium Threaded Interbody Fusion Device. These components must be used as
a system for the prescribed indication described below. The bone morphogenetic protein
solution component must not be used without the carrier/scaffold component or with a carrier/scaffold component different from the one described in this document. The INFUSE®
Bone Graft component must not be used without the Medtronic Titanium Threaded Interbody
Fusion Device component.
Medtronic Titanium Threaded Interbody Fusion Device component
LT-CAGE® Lumbar Tapered Fusion Device
The LT-CAGE® device consists of a hollow, perforated, machined cylinder with opposing flat sides.
The cage has a tapered design with an angle of 8.8° and is available in diameters ranging from
14mm to 18mm at the narrow end of the taper, 17mm to 22 mm at the wide end of the taper and in
lengths ranging from 20mm to 26mm. There are two holes on each of the two flat sides. On each
of the two rounded aspects, there is a single rounded slot. The implants have a helical screw thread
on the outer surface. One end of the device is closed. The other end is open to be filled with the
INFUSE® Bone Graft component.
The LT-CAGE® implants are made from implant grade titanium alloy (Ti-6Al-4V) described by such
standards as ASTM F136 or its ISO equivalent.
The LT-CAGE® Lumbar Tapered Fusion Device component is sold separately from the INFUSE®
Bone Graft component, however, these two components must be used together. The package labeling for the LT-CAGE® Lumbar Tapered Fusion Device contains complete product information for
this component.
INTER FIX™ Threaded Fusion Device
The INTER FIX™ device consists of a hollow, perforated, cylinder with parallel sides and an endcap. The cage is available in diameters ranging from 12mm to 24mm and in lengths ranging from
20mm to 29mm. The endcaps of the INTER FIX™ cages are sized according to the diameter of
the cylinders and are applied to the open end of the cylinders after they are filled with INFUSE®
Bone Graft.
The INTER FIX™ Threaded Fusion Device implants are made from implant grade titanium alloy
(Ti-6Al-4V) described by such standards as ASTM F136 or its ISO equivalent.
The INTER FIX™ Threaded Fusion Device component is sold separately from the INFUSE® Bone
Graft component; however, these two components must be used together. The package labeling for the INTER FIX™ Threaded Fusion Device contains complete product information for this
component.
INTER FIX™ RP Threaded Fusion Device
The INTER FIX™ RP device consists of a hollow, perforated, cylinder with a single, large, outer radiused groove along the entire longitudinal axis that extends into the inside diameter of the device.
Both ends of the INTER FIX™ RP implant are closed. The cage is available in diameters ranging from
12mm to 24mm and in lengths ranging from 20mm to 29mm.
The INTER FIX™ RP Threaded Fusion Device implants are made from implant grade titanium alloy
(Ti-6Al-4V) described by such standards as ASTM F136 or its ISO equivalent.
The INTER FIX™ RP Threaded Fusion Device component is sold separately from the INFUSE®
Bone Graft component; however, these two components must be used together. The package
labeling for the INTER FIX™ RP Threaded Fusion Device contains complete product information
for this component.
NOTE: The INTER FIX™ Threaded Fusion Device and the INTER FIX™ RP Threaded Fusion
Device may be used together to treat a spinal level. LT-CAGE® Lumbar Tapered Fusion Device
implants are not to be used in conjunction with either the INTER FIX™ OR INTER FIX™ RP
implants to treat a spinal level.
INFUSE® Bone Graft component
INFUSE® Bone Graft consists of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2,
known as dibotermin alfa) placed on an absorbable collagen sponge (ACS). The INFUSE® Bone
Graft component induces new bone tissue at the site of implantation. Based on data from nonclinical studies, the bone formation process develops from the outside of the implant towards the
center until the entire INFUSE® Bone Graft component is replaced by trabecular bone.
rhBMP-2 is the active agent in the INFUSE® Bone Graft component. rhBMP-2 is a disulfide-linked
dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit
is glycosylated at one site with high-mannose-type glycans. rhBMP-2 is produced by a genetically
engineered Chinese hamster ovary cell line.
rhBMP-2 and excipients are lyophilized. Upon reconstitution, each milliliter of rhBMP-2 solution
contains: 1.5 mg of rhBMP-2; 5.0 mg sucrose, NF; 25 mg glycine, USP; 3.7 mg L-glutamic acid,
FCC; 0.1 mg sodium chloride, USP; 0.1 mg polysorbate 80, NF; and 1.0 mL of sterile water. The
reconstituted rhBMP-2 solution has a pH of 4.5, and is clear, colorless and essentially free from
plainly visible particulate matter.
The ACS is a soft, white, pliable, absorbent implantable matrix for rhBMP-2. ACS is made from
bovine Type I collagen obtained from the deep flexor (Achilles) tendon. The ACS acts as a carrier for
the rhBMP-2 and acts as a scaffold for new bone formation.
The tables provided in the “Directions for Use” of this insert describe how to use the X Small
(1.4cc) and XX Small (0.7cc) kits to fill smaller single cages if the need arises during surgery.
For larger size cages, the following is recommended: If a Large kit was used originally to fill
two cages, use a Small plus an X Small (1.4cc) kit to fill a single cage; if a Medium kit was used
originally, use a Small kit to fill a single cage; if a Small kit was used originally, use an X Small
(1.4cc) kit to fill a single cage; and if an X Small (1.4cc) kit was used originally, use an XX Small
(0.7cc) kit to fill a single cage.
Each kit contains all the components necessary to prepare the INFUSE® Bone Graft component: the rhBMP-2 which must be reconstituted, sterile water, absorbable collagen sponge,
syringe(s) with needle(s), this package insert and instructions for preparation. The number of
each item may vary depending on the size of the kit. If two kits are going to be used (e.g., X
Small (1.4cc) & XX Small (0.7cc)), open both kits simultaneously and mix each according to
the directions.
The rhBMP-2 is provided as a lyophilized powder in vials delivering 1.05 mg of protein for the X
Small and XX Small kits. After appropriate reconstitution, the configuration results in the formulation and concentration (1.5 mg/mL) of rhBMP-2. The solution is then applied to the provided
absorbable collagen sponge. The INFUSE® Bone Graft component is prepared at the time of surgery and allowed a prescribed amount of time (no less than 15 minutes) before placement inside
of the Medtronic Titanium Threaded Interbody Fusion Device components. The Instructions for
Preparation contain complete details on preparation of the INFUSE® Bone Graft/Medtronic Titanium
Threaded Interbody Fusion Device.
Implied warranties of merchantability and fitness for a particular purpose or use are specifically
excluded. See the MDT Catalog or price list for further information about warranties and limitations
of liability.
INDICATIONS
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is indicated for
spinal fusion procedures in skeletally mature patients with degenerative disc disease (DDD) at one
level from L2-S1. DDD is defined as discogenic back pain with degeneration of the disc confirmed
by patient history and radiographic studies. These DDD patients may also have up to Grade I spondylolisthesis or Grade 1 retrolisthesis at the involved level. Patients receiving the INFUSE® Bone
Graft/Medtronic Titanium Threaded Interbody Fusion Device should have had at least six months
of nonoperative treatment prior to treatment with the INFUSE® Bone Graft/Medtronic Titanium
Threaded Interbody Fusion Device. The INFUSE® Bone Graft with the LT-CAGE® Lumbar Tapered
Fusion Device is to be implanted via an anterior open or an anterior laparoscopic approach. The
INFUSE® Bone Graft with either the INTER FIX™ or the INTER FIX™ RP Threaded Fusion Device is to
be implanted via an anterior open approach.
DIRECTIONS FOR USE
INFUSE® Bone Graft component is prepared at the time of surgery in the surgical suite by reconstituting the lyophilized rhBMP-2 with sterile water (See Instructions for Preparation), and then
uniformly applying the reconstituted rhBMP-2 solution to the ACS. The INFUSE® Bone Graft component is then inserted into the Medtronic Titanium Threaded Interbody Fusion Device component.
The complete device is then implanted through an anterior surgical approach (See the Surgical
Technique manual). If the INFUSE® Bone Graft component is not used within two hours after reconstitution, it must be discarded.
The INFUSE® Bone Graft component must not be sterilized by the hospital. The Medtronic Titanium
Threaded Interbody Fusion Device component, if not supplied sterile, should be sterilized before
insertion of the INFUSE® Bone Graft component. Please refer to the specific Medtronic Titanium
Threaded Interbody Fusion Device package insert for information on packaging, cleaning/decontamination and sterilization of this component and its instruments.
This insert describes only the use of the X Small (1.4cc) and XX Small (0.7cc) kit sizes of the
INFUSE® Bone Graft. See the insert for the other INFUSE® Bone Graft kits (Small, Medium, Large,
and Large II) for instructions for use on those size kits. The tables below list the appropriate X Small
(0.7cc) and XX Small (1.4cc) INFUSE® Bone Graft kit for the corresponding Medtronic Titanium
Threaded Interbody Fusion Device component size:
INFUSE® Bone Graft/INTER FIX™ Threaded Fusion Device Combinations
Dual INTER FIX™ Devices
INTER
Threaded
Fusion Device
Recommended INFUSE® Bone Graft Kit(s)
Size (diameter,
Reconstituted rhBMP-2/
Part #
Kit size
ACS graft volume (cc)
Part #
mm ∞ length, mm)
FIX™
890120
12 ∞ 20
7510100
X Small
1.4
890125
12 ∞ 25
7510050 +
7510100
XX Small +
X Small
2.1
INFUSE® Bone Graft/INTER FIX™ and INTER FIX™ RP Threaded Fusion Device Combinations
INTER FIX™ RP Device with INTER FIX™ Device
INTER FIX™ and INTER FIX™ RP
Recommended INFUSE® Bone Graft Kit(s)
Threaded Fusion Devices
Part # of
Size (diameter,
INTER FIX™
Reconstituted rhBMP-2/
Devices**
mm ∞ length, mm)
Part #
Kit size
ACS graft volume (cc)
890120 +
7510100
X Small
1.4
12 ∞ 20
9011221
7510050 +
XX Small +
890125 +
2.1
12 ∞ 25
7510100
X Small
9011225
** The INTER FIX™ Threaded Fusion Device is to be used with the corresponding size of the INTER FIX™ RP
Threaded Fusion Device.
INFUSE® Bone Graft/INTER FIX™ RP Threaded Fusion Device Combinations
Dual INTER FIX™ RP Devices
INTER FIX™ RP
Threaded Fusion Device
Recommended INFUSE® Bone Graft Kit(s)
Size (Diameter,
Reconstituted rhBMP-2/
Part #
Kit size
ACSgraft volume (cc)
Part #
mm ∞ length, mm)
9011221
12 ∞ 20
7510100
X Small
1.4
9011225
12 ∞ 25
7510050 +
7510100
XX Small +
X Small
2.1
WARNINGS
•
In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are capable
of crossing the placenta. Reduced ossification of the frontal and parietal bones of the skull was
noted infrequently (<3%) in fetuses of rabbit dams immunized to rhBMP-2; however, there
was no effect noted in limb bud development. There are no adequate and well-controlled studies in human pregnant women. Women of child bearing potential should be warned by their
surgeon of potential risk to a fetus and informed of other possible orthopedic treatments.
•
Women of childbearing potential should be advised that antibody formation to rhBMP-2
or its influence on fetal development has not been completely assessed. In the clinical trial
supporting the safety and effectiveness of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device, 2/277 (0.7%) patients treated with INFUSE® Bone Graft component
and 1/127 (0.8%) patients treated with autograft bone developed antibodies to rhBMP-2.
The effect of maternal antibodies to rhBMP-2, as might be present for several months
following device implantation, on the unborn fetus is unknown. Additionally, it is unknown
whether fetal expression of BMP-2 could re-expose mothers who were previously antibody
positive. Theoretically, re-exposure may elicit a more powerful immune response to BMP-2
with possible adverse consequences for the fetus. However, pregnancy did not lead to an
increase in antibodies in the rabbit study. Studies in genetically altered mice indicate that
BMP-2 is critical to fetal development and that a lack of BMP-2 activity may cause neonatal
death or birth defects. It is not known if anti-BMP-2 antibodies may affect fetal development or the extent to which these antibodies may reduce BMP-2 activity.
•
INFUSE® Bone Graft should not be used immediately prior to or during pregnancy. Women of
childbearing potential should be advised not to become pregnant for one year following treatment with the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device.
•
The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device in nursing mothers has not been established. It is not known if
BMP-2 is excreted in human milk.
SINGLE CAGE USE
In the case of only one cage needing INFUSE® Bone Graft, due to the loss or contamination of a
sponge or sponges, single cages can be filled using the X Small (1.4cc) and/or XX Small (0.7cc)
kits as shown below:
INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations
Single LT-CAGE® Device Fill
LT-CAGE®
Lumbar Tapered Fusion Device
Recommended INFUSE® Bone Graft Kit(s)
Size (lead diameter,
Reconstituted rhBMP-2/
Part #
Kit size
ACS graft volume (cc)
Part #
mm ∞ length, mm)
8941420
14 ∞ 20
7510100
X Small
1.4
8941423
14 ∞ 23
7510100
X Small
1.4
8941620
16 ∞ 20
8941623
16 ∞ 23
7510050 +
7510100
7510050 +
7510100
XX Small +
X Small
XX Small +
X Small
2.1
2.1
INFUSE® Bone Graft/INTER FIX™ Threaded Fusion Device Combinations
Single INTER FIX™ Device Fill
INTER FIX™
Threaded Fusion Device
Recommended INFUSE® Bone Graft Kit(s)
Size (diameter,
Reconstituted rhBMP-2/
Part #
Kit size
ACS graft volume (cc)
Part #
mm ∞ length, mm)
890120
12 ∞ 20
7510050
XX Small
0.7
890125
12 ∞ 25
7510100
X Small
1.4
890140
14 ∞ 20
7510100
X Small
1.4
890143
14 ∞ 23
7510100
X Small
1.4
890146
14 ∞ 26
890149
14 ∞ 29
890160
16 ∞ 20
890163
16 ∞ 23
7510050 +
7510100
7510050 +
7510100
7510050 +
7510100
7510050 +
7510100
XX Small +
X Small
XX Small +
X Small
XX Small +
X Small
XX Small +
X Small
– When anterior cervical spinal fusions were performed using the INFUSE® Bone Graft component, some cases of edema have been reported within the first post-operative week. In
some of these cases, this swelling has been severe enough to produce airway compromise,
sometimes requiring emergency surgery.
2.1
•
The implantation of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device using
an anterior laparoscopic surgical approach is associated with a higher incidence of retrograde
ejaculation when compared to implantation using an anterior open surgical approach.
•
Inappropriate use of the product, such as preparing it differently than prescribed, compressing
the rhBMP-2/ACS implant more than necessary, or overfilling the volume intended for new bone
formation, may change the concentration of the rhBMP-2, which may inhibit the ability of the
rhBMP-2/ACS to convert to bone and/or cause complications. Such use of the rhBMP-2/ACS
implant may result in radiographic evidence of resorption, fluid formation, and/or edema. These
findings may be asymptomatic or symptomatic.
•
While there are currently anecdotal and literature evidence to suggest that volume overfilling
and/or hyperconcentration of the rhBMP-2 solution may lead to fluid formation and/or edema,
animal models for scientifically evaluating these events do not presently exist. A sheep model developed to test the hypothesis that volume overfilling and/or hyperconcentration of the
rhBMP-2 solution results in radiographic evidence of bone resorption has preliminarily been
evaluated and appears to be supportive of the hypothesized mechanism.
2.1
•
Placement of rhBMP-2/ACS can cause initial resorption of trabecular bone that may be transient.
2.1
•
Nerve compression associated with ectopic bone formation has been reported in patients undergoing
spine surgery with rhBMP-2/ACS. Surgical intervention may be required to address the symptoms.
2.1
2.1
9011221
12 ∞ 20
7510050
XX Small
0.7
9011225
12 ∞ 25
7510100
X Small
1.4
9011420
14 ∞ 20
7510100
X Small
1.4
9011423
14 ∞ 23
7510100
X Small
1.4
9011426
14 ∞ 26
9011429
14 ∞ 29
9011620
16 ∞ 20
9011623
16 ∞ 23
7510050 +
7510100
7510050 +
7510100
7510050 +
7510100
7510050 +
7510100
XX Small +
X Small
XX Small +
X Small
XX Small +
X Small
XX Small +
X Small
2.1
2.1
CONTRAINDICATIONS
• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is contraindicated for patients with a known hypersensitivity to recombinant human Bone Morphogenetic
Protein-2, bovine Type I collagen or to other components of the formulation.
•
The safety and effectiveness of the use of the INFUSE® Bone Graft component with other spinal
implants, implanted at locations other than the lower lumbar spine, or used in surgical techniques other than anterior open (LT-CAGE®, INTER FIX™, INTER FIX™ RP devices) or anterior
laparoscopic (LT-CAGE® device) approaches have not been established.
– When degenerative disc disease was treated by a posterior lumbar interbody fusion procedure with cylindrical threaded cages (INTER FIX™ devices), posterior bone formation
was observed in some instances.
2.1
INFUSE® Bone Graft/INTER FIX™ RP Threaded Fusion Device Combinations
Single INTER FIX™ RP Device Fill
INTER FIX™
Threaded Fusion Device
Recommended INFUSE® Bone Graft Kit(s)
Size (diameter,
Reconstituted rhBMP-2/
Part #
Kit size
ACS graft volume (cc)
Part #
mm ∞ length, mm)
•
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
used in the vicinity of a resected or extant tumor, in patients with any active malignancy or
patients undergoing treatment for a malignancy.
INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be used
in patients who are skeletally immature (<18 years of age or no radiographic evidence of epiphyseal closure).
PRECAUTIONS
PHYSICIAN NOTE: Although the physician is the learned intermediary between the company and the
patient, the important medical information given in this document should be conveyed to the patient.
!USA
For US audiences only
General
• The safety and effectiveness of repeat applications of the INFUSE® Bone Graft component has
not been established.
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should only
be used by surgeons who are experienced in spinal fusion procedures and have undergone
adequate training with this device, for anterior laparoscopic and/or anterior open procedures.
•
Two Medtronic Titanium Threaded Interbody Fusion Device components should be implanted
side by side at the surgical level whenever possible.
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in pregnant women. The potential effects of rhBMP-2 on the human fetus have not
been evaluated.
•
The Medtronic Titanium Threaded Interbody Fusion Device components and instruments must
be sterilized prior to use according to the sterilization instructions provided in the package insert
for that component, unless supplied sterile and clearly labeled as such.
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
implanted in patients with an active infection at the operative site or with an allergy to titanium
or titanium alloy.
•
When using this device at spinal levels between L2 and L4, the potential impact of anatomical
structures, e.g., the aorta, on implant placement must be considered.
•
The formation of exuberant or ectopic bone growth at the upper lumbar levels (L2- L4) may have a
deleterious impact on certain neurovascular structures, e.g., the aorta and sympathetic nerve chain.
•
The safety and effectiveness of the device at spinal levels L2 - L4 or in patients with up to Grade
1 retrolisthesis has not been established.
•
The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is intended for
single use only. Discard unused product and use a new device for subsequent applications.
•
Prior to use, inspect the packaging, vials and stoppers for visible damage. If damage is
visible, do not use the product. Retain the packaging and vials and contact a Medtronic
representative.
•
Do not use after the printed expiration date on the label.
Hepatic and Renal Impairment
• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device in patients with hepatic or renal impairment has not been established. Pharmacokinetic
studies of rhBMP-2 indicate that the renal and hepatic systems are involved with its clearance.
Geriatrics
• Clinical studies of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device did not
include sufficient numbers of patients 65 years and older to determine whether they respond
differently from younger subjects.
Bone formation
• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with metabolic bone diseases.
•
While not specifically observed in the clinical study, the potential for ectopic, heterotopic or
undesirable exuberant bone formation exists.
Antibody Formation/Allergic Reactions
• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with autoimmune disease.
•
The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with immunosuppressive disease or suppressed immune systems resulting from radiation therapy, chemotherapy, steroid therapy or
other treatments.
Immunogenicity
• As with all therapeutic proteins, there is a potential for immune responses to be generated to
the INFUSE® Bone Graft component. The immune response to the INFUSE® Bone Graft components was evaluated in 349 investigational patients and 183 control patients receiving lumbar
interbody fusions.
– Anti-rhBMP-2 antibodies: 2/349 (0.6%) patients receiving the INFUSE® Bone Graft component developed antibodies vs. 1/183 (0.5%) in the control group.
– Anti-bovine Type I collagen antibodies: 18.1% of patients receiving the INFUSE® Bone Graft
component developed antibodies to bovine Type I collagen vs. 14.2% of control patients. No
patients in either group developed anti-human Type I collagen antibodies.
•
The presence of antibodies to rhBMP-2 was not associated with immune mediated adverse events
such as allergic reactions. The neutralizing capacity of antibodies to rhBMP-2 is not known.
•
The incidence of antibody detection is highly dependent on the sensitivity and specificity of the
assay. Additionally, the incidence of antibody detection may be influenced by several factors
including sample handling, concomitant medications and underlying disease. For these reasons,
comparison of the incidence of antibodies to the INFUSE® Bone Graft component with the incidence of antibodies to other products may be misleading.
ADVERSE EVENTS
The INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device was implanted in 288 investigational patients and compared to 139 control patients who received an LT-CAGE® Lumbar Tapered
Fusion Device filled with iliac crest autograft. The investigational patients were implanted with the
device via either an open anterior surgical approach or a laparoscopic anterior surgical approach.
The control patients were implanted only via the open anterior surgical approach.
Adverse event rates presented are based on the number of patients having at least one occurrence
for a particular adverse event divided by the total number of patients in that treatment group. Because no control subjects were evaluated at the 48 and 72 month timepoints, the reported events at
these timepoints are only from the investigational subjects.
ADVERSE EVENTS
(INFUSE® Bone Graft/LT-CAGE® Device data combined from all experience with the device)
Postoperative
(1 day <4 Weeks)
Surgery
6 Weeks
(≥4 Weeks <9 Weeks)
3 Months
(≥9 Weeks <5 Months)
6 Months
(≥5 Months <9 Months)
12 Months
(≥9 Months <19 Months)
24 Months
(≥19 Months <30 Months)
Inves.
Control
Inves.
Control
Inves.
Control
Inves.
Control
Inves.
Control
Inves.
Control
Inves.
Control
Anatomical/Technical
Difficulty
11
3
0
0
0
0
0
0
0
0
0
0
0
0
Back and/or Leg Pain
0
0
12
4
11
5
12
5
8
11
20
7
8
11
Complication
Cancer
0
0
0
0
0
0
0
1
1
0
1
0
1
0
Cardio/Vascular
1
0
6
5
5
2
1
3
1
1
4
2
1
1
Death
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Dural Injury
0
0
0
0
0
0
0
1
0
0
0
0
0
0
Gastrointestinal
1
0
40
22
2
0
5
1
7
5
10
3
7
5
Graft Site Related
0
0
0
8
0
0
0
0
0
0
0
0
0
0
Implant
Displacement/
Loosening
0
0
1
1
3
0
1
0
0
0
0
0
0
0
Infection
0
0
19
9
8
4
5
1
0
2
3
0
0
2
Malpositioned Implant
5
0
0
0
0
0
0
0
0
0
0
0
0
0
Neurological
0
0
8
5
7
3
5
2
6
8
13
4
6
8
Non-Union*
0
0
0
0
0
0
0
0
1
1
4
0
1
1
Non-Union**
0
0
0
1
0
1
2
0
1
1
4
6
1
1
Other
5
6
18
11
9
2
3
4
20
7
15
8
20
7
Other Pain
0
0
3
1
2
1
4
2
10
3
11
8
10
3
Respiratory
0
0
3
2
1
0
0
0
0
1
0
1
0
1
Retrograde Ejaculation
0
0
5
1
4
0
1
0
0
0
2
0
0
0
Spinal Event
0
0
1
2
1
0
6
2
9
2
10
8
9
2
Subsidence
0
0
3
2
2
0
1
0
0
0
0
0
0
0
Trauma
0
0
4
5
5
3
11
7
19
8
28
11
19
8
Urogenital
0
0
24
5
3
0
2
3
7
2
3
1
7
2
Vascular Intra-Op
15
5
0
0
0
0
0
0
0
0
0
0
0
0
Vertebral Fracture
0
0
1
0
0
0
0
0
0
0
0
0
0
0
Any Adverse Event
* Non-union adverse events that have not resulted in a second surgery.
** Non-union adverse events that have resulted in a second surgery.
1 Percent of 140 males.
2 Percent of 70 males.
# of Patients Reporting &
Total adverse events
48 Months
(≥30 Months <60 Months)
72 Months
(≥60 Months <84 Months)
Investigational
# (% of 288)
total events
Control
#(% of 139)
total events
Total #
(% of 134)
total events
Total #
(% of 140)
total events
11 (3.8)
11
70 (24.3)
78
2 (0.7)
2
17 (5.9)
20
0 (0.0)
0
0 (0.0)
0
56 (19.4)
72
0 (0.0)
0
3 (2.2)
3
36 (23.0)
32
1 (0.7)
1
12 (8.6)
14
1 (0.7)
1
1 (0.7)
1
27 (19.4)
32
8 (5.8)
8
0 (0.0)
0
22 (16.4)
23
4 (3.0)
4
7 (5.2)
7
2 (1.5)
2
0 (0.0)
0
14 (10.4)
17
0 (0.0)
0
0 (0.0)
0
18 (12.9)
21
1 (0.7)
1
4 (2.9)
4
0 (0.0)
0
0 (0.0)
0
6 (4.3)
8
0 (0.0)
0
5 (1.7)
5
1 (0.7)
1
0 (0.0)
0
0 (0.0)
0
36 (12.5)
40
5 (1.7)
5
39 (13.5)
45
6 (2.1)
6
10 (3.5)
10
64 (22.2)
81
31 (10.8)
36
5 (1.7)
5
11 (7.9)1
12
30 (10.4)
37
7 (2.4)
7
69 (24.0)
81
41 (14.2)
45
14 (4.9)
15
1 (0.3)
1
235 (81.6)
16 (11.5)
17
0 (0.0)
0
23 (16.5)
24
3 (2.2)
3
13 (9.4)
13
37 (26.6)
42
14 (10.1)
1
4 (2.9)
4
1 (1.4)2
1
17 (12.2)
18
2 (1.4)
2
34 (24.5)
39
13 (9.4)
14
5 (3.6)
5
0 (0.0)
0
121 (87.1)
4 (3.0)
4
0 (0.0)
0
12 (9.0)
12
0 (0.0)
0
0 (0.0)
0
22 (16.4)
29
14 (10.4)
19
1 (0.7)
1
0 (0.0)
0
9 (6.7)
9
0 (0.0)
0
21 (15.7)
23
2 (1.5)
2
1 (0.7)
1
0 (0.0)
0
84 (62.7)
3 (2.1)
3
0 (0.0)
0
5 (3.6)
5
0 (0.0)
0
0 (0.0)
0
17 (12.1)
18
12 (8.6)
13
0 (0.7)
1
0 (0.0)
0
8 (5.7)
8
0 (0.0)
0
20 (14.3)
22
3 (2.1)
3
0 (0.0)
0
0 (0.0)
0
64 (45.7)
The reported rates of several adverse events were high, but similar, in both the investigational
and control groups. These events included back and leg pain, neurological events, gastrointestinal
events, spinal events, cardiovascular events and infection.
jects rate their outcome using objective self-assessments. The radiographic outcome parameters
were performed by independent radiologists who were blinded to treatment. These were the only
radiographic evaluations used for determining radiographic success.
Some of the reported adverse events required surgical interventions subsequent to the initial surgery. The number of subjects requiring a second surgical intervention was 10.4% (30/288) in the
investigational groups and 13.7% (19/139) in the control group. The majority of supplemental fixations were due to painful non-union.
The indication studied was degenerative disc disease (DDD) accompanied by back pain with or
without leg pain at a single level between L4 and S1 confirmed by history and radiographic studies.
Urogenital events occurred with greater frequency in the investigational groups (11.5%) compared
to the control group (7%). Retrograde ejaculation rates were greater in the investigational groups
(11 subjects) compared to the control group (1 subject) with the majority of events occurring in the
early postoperative period.
The incidence of adverse events that were considered device related, including implant displacement/loosening, implant malposition and subsidence were all greater in the investigational groups
compared to the control group. The rates of these events were low, however, and may be partially
attributed to a learning curve associated with the laparoscopic surgical approach. The rate of nonunion requiring secondary surgery in the investigational groups was comparable to that of the
control group. One death was reported - a control group subject with cardiovascular disease.
Potential Adverse Events
The following is a list of potential adverse events which may occur with spinal fusion surgery with
the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device. Some of these
adverse events may have been previously reported in the adverse events table or have been reported
to the manufacturer:
• Bone fracture.
• Bowel or bladder problems.
• Cessation of any potential growth of the operated portion of the spine. Loss of spinal mobility or
function.
• Change in mental status.
• Damage to blood vessels and cardiovascular system compromise.
• Damage to internal organs and connective tissue.
• Death.
• Development of respiratory problems.
• Disassembly, bending, breakage, loosening, and/or migration of components.
• Dural tears.
Clinical and radiographic effectiveness parameters
Patients were evaluated preoperatively (within 6 months of surgery), intraoperatively, and postoperatively at 6 weeks, 3, 6, 12 and 24 months and biennially thereafter until the last subject enrolled in the
study had been seen for their 24 month evaluation. Complications and adverse events, device-related
or not, were evaluated over the course of the clinical trial. At each evaluation timepoint, the primary
and secondary clinical and radiographic outcome parameters were evaluated. Success was determined from data collected during the initial 24 months of follow-up. Antibodies to rhBMP-2 and bovine
Type I collagen were assessed preoperatively and at 3 months post-operatively. Antibodies to human
Type I collagen were assessed if the antibody response to bovine Type I collagen was positive.
Primary and secondary clinical and radiographic effectiveness outcome parameters were evaluated for all treated subjects at all follow-up evaluation timepoints identified above. The primary
clinical parameters assessed were of pain, function and neurological status. The secondary clinical outcome parameters assessed were general health status, back and leg pain, donor site pain
(control subjects only), patient satisfaction and patient global perceived effect of the treatment. The
primary radiographic outcome parameter consisted of evaluations of fusion, while the secondary
radiographic assessment was disc height.
Fusion was evaluated at 6, 12 and 24 months post-op using plain radiographs (AP, lateral and
flexion/extension films) and high resolution thin-slice CT scans (1mm slices with 1mm index on
axial sagittal and coronal reconstructions). Fusion was defined as the presence of bridging bone
connecting the inferior and superior vertebral bodies; a lack of motion on flexion/extension (≤ 3mm
of translation and < 5° of angulation); and no evidence of radiolucencies over more than 50% of
either implant. Fusion success was defined as the presence of all of these parameters plus the lack
of a second surgical intervention resulting from a non-union. All assessments were made from the
plain films except for the assessment of bridging bone, which was made using the CT scans only if
bridging bone could not be visualized on the plain film.
Pain and function were measured using the Oswestry Low Back Pain Disability Questionnaire. Success was defined as a 15 point improvement in the Oswestry score from the pre-op baseline score.
Neurological status consisted of measurements of four parameters - motor, sensory, reflexes, and
straight leg raise (SLR). Neurological status success was defined as maintenance or improvement
of the pre-op baseline score for each parameter. Overall neurological status success required that
each individual parameter be a success for that subject to be counted as a success.
• Foreign body (allergic) reaction.
Patient demographics and accountability
A total of 143 open approach investigational and 136 control patients were enrolled in the randomized arm of the study and received the device. A total of 134 subjects were enrolled in the non-randomized arm of the study and received the device. For the majority of the demographic parameters,
there were no differences in pre-op demographics across the three populations.
• Gastrointestinal complications.
Surgical results and hospitalization
• Ectopic and/or exuberant bone formation.
• Fetal development complications.
Surgical and hospitalization information
• Incisional complications.
• Infection.
• Insufflation complications.
• Neurological system compromise.
• Non-union (or pseudarthrosis), delayed union, mal-union.
• Postoperative change in spinal curvature, loss of correction, height, and/or reduction.
Investigational Open
Surgical Approach
mean operative time (hrs)
1.6*
mean EBL (ml)
109.8*
Hospitalization (days)
3.1
*statistically different from control
Control Open Surgical
Approach
2.0
153.1
3.3
Investigational
Laparoscopic Surgical
Approach
1.9
146.1
1.2*
• Scar formation.
Clinical and radiographic effectiveness evaluation
Individual subject success was defined as success in each of the primary clinical and radiographic
outcome parameters. Success for these parameters included:
• Tissue or nerve damage.
1. the presence of radiographic fusion;
• Edema (swelling).
2. an improvement of at least 15 points from the baseline Oswestry score;
• Inflammation.
3. maintenance or improvement in neurological status;
• Erythematous tissue.
• Allergic reaction.
4. the presence of no serious adverse event classified as implant-associated or implant/surgical
procedure-associated; and
• Itching.
5. no additional surgical procedure classified as “Failure.”
• Anaphylactic reaction.
Study success was expressed as the number of individual subjects categorized as a success divided
by the total number of subjects evaluated. The table below describes the success rates for the
individual primary outcome parameters and overall success. All success rates were based on the
data from the 24 month follow-up evaluation and posterior probabilities of success were calculated
using Bayesian statistical methods.
• Retrograde ejaculation.
• Elevated erythrocyte sedimentation rate.
• Pain.
• Hematoma.
Note: Additional surgery may be necessary to correct some of these potential adverse events.
CLINICAL RESULTS
Clinical data to support the safety and effectiveness of the INFUSE® Bone Graft/ LT-CAGE®
Lumbar Tapered Fusion Device were collected as part of a prospective, multi-center pivotal
study that consisted of randomized and non-randomized arms. The randomized arm contained
two groups, one investigational and one control. The control group was implanted with the
LT-CAGE® Lumbar Tapered Fusion Device filled with iliac crest autograft bone, while the investigational group was implanted with the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered
Fusion Device. In both cases, the surgical approach was an open anterior approach. The nonrandomized arm contained only an investigational group, where subjects were implanted with
the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device through a laparoscopic anterior approach. The control group from the randomized arm was used as the control for the
non-randomized arm.
Neither the investigators nor the subjects were blinded to the treatment. Subject blinding was not
possible due to the second surgical site resulting from the need to collect the iliac crest grafts. The
potential for investigator bias in the clinical outcome parameters was reduced by having the sub-
Primary
outcome
variable
Fusion
Oswestry
Neurologic
Overall
success
Posterior Probabilities of Success at 24 Months
Investigational Open
Control Open
Investigational Laparoscopic
Surgical Approach
Surgical Approach
Surgical Approach
Posterior Mean
Posterior Mean
Posterior Mean
(95% HPD Credible
(95% HPD Credible
(95% HPD Credible
Interval)
Interval)
Interval)
92.8%
88.1%
93.0%
(88.5%, 96.9%)
(82.6%, 99.3%)
(87.9%, 97.5%)
71.0%
70.9%
83.0%
(63.4%, 78.7%)
(63.1%, 79.1%)
(75.6%, 90.5%)
81.0%
81.7%
89.0%
(74.5%, 87.9%)
(74.9%, 88.7%)
(83.1%, 94.8%)
57.1%
56.7%
68.0%
(49.2%, 65.7%)
(48.3%, 65.0%)
(59.3%, 76.5%)
The probability (also called the posterior probability) that the 24 month overall success rate for
the investigational groups was equivalent to the 24 month success rate for the control group was
99.4% for the open surgical approach investigational group and almost 100% for the laparoscopic
surgical approach investigational group.
For a future patient receiving the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device via
the open anterior surgical approach, the chance (the predictive probability) of overall success at 24
months would be 57.1% for the open surgical approach. Given the results of the trial, there is a 95%
probability that the chance of success ranges from 49.2% to 65.7%. For a future patient receiving
the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device via the anterior laparoscopic
surgical approach, the chance of overall success at 24 months would be 68.0%. Given the results
of the trial, there is a 95% probability that the chance of success ranges from 59.3% to 76.5%. For
a future patient receiving the control treatment, the chance of overall success at 24 months would
be 56.7%. Given the results of the trial, there is a 95% probability that the chance of success ranges
from 48.3% to 65.0%.
cal technique manuals for the INFUSE® Bone Graft with the specific Medtronic Titanium Threaded
Interbody Fusion Devices referenced in this package insert are available and will provide more
information on templating to determine the appropriate size Medtronic Titanium Threaded Interbody
Fusion Device component.
Safety and immune response evaluation
The assessment of safety consisted of an evaluation of the reported adverse events, as well as an
evaluation of antibodies to rhBMP-2, bovine Type I collagen and human Type I collagen. The complete list of complications, adverse events and subsequent interventions is described in the Adverse
Events section above. The presence of antibodies was assessed at the pre-op and 3 month post-op
visits using ELISA. If there was a positive response to bovine Type I collagen, the serum was also
tested for antibodies to human Type I collagen. The screening ELISA cutpoint for positive antibody
responses was set to 5 times the standard deviation of sera from normal human donors. Subjects
were considered to have an elevated immune response if the preoperative test was negative (titer <
50) and postoperative test was positive (titer ≥ 50) or if the preoperative test was positive and the
postoperative test was positive with a three-fold higher titer than the preoperative test.
PRODUCT COMPLAINTS
Any Health Care Professional (e.g., customer or user of this system of products), who has any complaints or who has experienced any dissatisfaction in the product quality, identity, durability, reliability, safety, effectiveness and/or performance, should notify the distributor or Medtronic. Further,
if any of the implanted INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device
component(s) ever “malfunctions,” (i.e., do not meet any of their performance specifications or otherwise do not perform as intended), or are suspected of doing so, the distributor should be notified
immediately. If any Medtronic product ever “malfunctions” and may have caused or contributed to
the death or serious injury of a patient, the distributor should be notified immediately by telephone,
fax or written correspondence. When filing a complaint, please provide the component(s) name
and number, lot number(s), your name and address, the nature of the complaint and notification of
whether a written report from the distributor is requested.
There were 3 subjects who had positive antibody responses to rhBMP-2 – 1 subject in each of the
study groups. The rates of positive antibody response to rhBMP-2 were 0.7% in the open surgical
approach investigational group and 0.8% in the laparoscopic surgical approach investigational and
open surgical approach control groups. While there is a theoretical possibility that antibodies to
rhBMP-2 could neutralize endogenous BMP-2, thereby interfering with subsequent bone healing,
this was not observed during the course of the study.
Sixty-six subjects were considered to have an authentic elevated antibody response to bovine Type
I collagen - 18 open surgical approach investigational subjects, 32 laparoscopic surgical approach
investigational subjects and 16 control subjects. No subjects had positive responses to human
Type I collagen.
An evaluation was performed on the impact of a positive antibody response on overall success and
fusion success. There was very little difference in overall and individual success when antibody
status was taken into consideration.
During the course of the study, 6 pregnancies were reported – one in the control group and five in
the investigational groups. Two of the four pregnancies that occurred in the laparoscopic approach
group resulted in first trimester miscarriages. The other three pregnancies in the investigational
groups resulted in live births with no reported complications. None of the pregnant subjects had
antibody responses to rhBMP-2 or Type I collagen (bovine or human), that were detectable to the
limits of the sensitivity of the assay.
Two cases of cancer were diagnosed during the course of the pivotal study – one in an investigational group and one in the control group. An investigational subject was found to have pancreatic
cancer while a control subject was found to have breast cancer. No additional information is available on these subjects, e.g., BMP-2 receptor expression.
Post-Approval Study
A total of 145 investigational subjects were evaluated out to 6 years (72 months) after the initial
surgery in a post-approval study. The patient population was obtained from participants in both the
open and laparoscopic arms of the IDE clinical trial. Control subjects from the IDE study were not
followed in the post-approval study. Based on criteria from the IDE study, information pertaining
to the safety and effectiveness of the product was obtained at four and six years post-implantation,
including adverse events, an independent radiographic assessment of fusion, and an assessment of
pain and function. The table below summarizes the clinical and radiographic data evaluated during
the post approval study, as well as the overall success rate at each timepoint.
Overall Success Rates – Post Approval Study
Variable
4-Year Evaluation
Overall Success
60.6% (77/127)
Oswestry Pain Improvement
81.5% (106/130)
Fusion
98.3% (117/119)
Neurological Status
73.3% (96/131)
(Maintenance or Improvement)
6-Year Evaluation
60.4% (84/139)
79.0% (109/138)
98.5% (128/130)
81.2% (112/138)
HOW SUPPLIED
INFUSE® Bone Graft component is supplied in five kit sizes containing all the components
necessary to prepare this portion of the device, i.e., the collagen sponge(s), a vial with the
lyophilized growth factor, a vial with sterile water for reconstituting the growth factor, syringes
and needles. This insert describes only the use of two kit sizes, the X Small (1.4cc) and XX
Small (0.7cc) of the INFUSE® Bone Graft. The Medtronic Titanium Threaded Interbody Fusion
Device component is supplied in a variety of sizes which must be properly selected based on
a specific patient’s anatomy.
STORAGE CONDITIONS
Store the INFUSE® Bone Graft component at room temperature [15-30 degrees Centigrade (59
to 86° F)]. The Medtronic Titanium Threaded Interbody Fusion Device component should also be
stored at room temperature.
DOSAGE AND ADMINISTRATION
INFUSE® Bone Graft component is prepared immediately prior to use from a kit containing all
necessary components. Once prepared, the INFUSE® Bone Graft component contains rhBMP-2 at
a concentration of 1.5 mg/mL.
The size of the INFUSE® Bone Graft component kit and the volume of INFUSE® Bone Graft component to be implanted are determined by the internal volume of the Medtronic Titanium Threaded
Interbody Fusion Device components which are utilized. The patient’s anatomy will determine the
size of the Medtronic Titanium Threaded Interbody Fusion Device components to be used. Surgi-
Only store the components in this INFUSE® Bone Graft kit in the manner described on the package,
only mix the components in the manner described in the directions, only add the reconstituted
rhBMP-2 to the ACS carrier provided in the manner described, and only use in the quantity and
indication specified in the package insert. Any other storage, mixture, or administration may cause
unanticipated adverse events.
DEVICE RETRIEVAL EFFORTS
Should it be necessary to remove an INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device, please call Medtronic prior to the scheduled surgery to receive instructions regarding data collection, including histopathological, mechanical and adverse event information.
In USA
Customer Service Division
Telephone:
Medtronic Sofamor Danek USA, Inc.
1800 Pyramid Place
Memphis, Tennessee 38132
USA
Telefax:
800-933-2635
800-876-3133
or 901 396 3133
901 396 0356
Supplied by
Medtronic Sofamor Danek USA, Inc.
©2008 Medtronic Sofamor Danek, Inc. All rights reserved.
INFUSE® Bone Graft in combination with LT-CAGE, INTER FIX™ or INTER FIX™ RP devices
incorporate technology developed by Gary K. Michelson, M.D.
The surgical technique shown is for illustrative purposes only. The technique(s) actually employed in each case will always depend
upon the medical judgment of the surgeon exercised before and during surgery as to the best mode of treatment for each patient.
Please see the package insert for the complete list of indications, warnings, precautions, and other medical information.
MEDTRONIC
Spinal and Biologics Business
Worldwide Headquarters
2600 Sofamor Danek Drive
Memphis, TN 38132
1800 Pyramid Place
Memphis, TN 38132
(901) 396-3133
(800) 876-3133
Customer Service: (800) 933-2635
www.sofamordanek.com
For more information go to www.myspinetools.com
MLITINFLTOST8
IRN1584/046 REVIRN7182/068
©2008 Medtronic Sofamor Danek USA, Inc.
All Rights Reserved.