INFUSE BONE GRAFT PRECLINICAL AND CLINICAL EVIDENCE: SPINAL FUSION Bone Grafting (Spine and Orthopaedic)

EVIDENCE – SPINAL FUSION

View data in three categories:

  • Level 1 clinical evidence
    A 279-patient multi-center study found no statistical difference in patients treated with autogenous iliac crest bone graft compared to those treated with Infuse™ Bone Graft
  • Preclinical studies
    Lower- and higher-order animal studies examined spinal fusion facilitated by recombinant human bone morphogenetic protein-2 (rhBMP-2), both in achieving fusion and in determining the appropriate amount of the protein.

Level 1 Clinical Evidence1

Clinical data compared patients who received Infuse Bone Graft versus autograft for lumbar fusion. Infuse Bone Graft results indicate it heals patients as well as autograft. It also saves patients from the pain and complications of the secondary bone harvesting procedure required for autograft. The results also show that Infuse Bone Graft saved hospitals money by avoiding this secondary procedure.

Traditional lumbar fusion using autograft presents many limitations. It may require an additional surgery to harvest iliac crest autograft, including its associated morbidity. The available autograft may be limited (especially in minimally invasive techniques) or of poor quality.

To weigh autograft against Infuse Bone Graft used in conjunction with an LT-Cage™ device (at a single level), a prospective, randomized clinical trial compared the two. Of the 279 patients in the multi-center study:

  • 136 patients were treated with autogenous iliac crest bone graft.
  • 143 patients were treated with Infuse Bone Graft.

There was no statistical difference in demographics between investigational and control groups. The study enrollment included challenging/hard-to-heal patients:

  • Over 32% in both groups were workers’ compensation patients.
  • Over 12% in both groups were in spinal litigation.
  • Over 32% in both groups were tobacco users.

 

Autograft

Infuse Bone Graft

N

136

143

Age (yrs.)

42.3

43.3

Weight (lbs.)

181.1

179.1

Sex (Male/Female)

68/68

78/65

Workers' Compensation (%)

34.6

32.9

Spinal Litigation (%)

16.2

12.6

Tobacco Use (%)

36.0

32.9

History of Previous Surgeries

40.4

37.8

The study had greater than 90% accountability at 24 months, with Infuse Bone Graft patients at 92.5% and autograft patients at 90.8%. The high patient accountability at each of the time intervals validates the study results.

The study had greater than 90% accountability at 24 months, validating study results.

High Fusion Rates at 12 and 24 Months1

Fusion was assessed using radiograph and CT scans with sagittal and coronal reconstruction. The results indicated at 24 months, Infuse Bone Graft fusion rate was 94.5%, a higher percentage than the 88.7% fusion rate of the control group (though statistically equivalent).

At 24 months, Infuse Bone Graft fusion rate was 94.5%, a higher percentage than the 88/7% fusion rate of the control group.

Comparison of Autograft Versus Infuse Bone Graft Patients1

Infuse Bone Graft matched the ability of autograft to reduce pain and disability. Compared to preoperative scores, Infuse bone graft patients indicated a 55% improvement on average.

Infuse Bone Graft matched the ability of autograft to reduce pain and disability.

Infuse Bone Graft eliminates hip pain and the complications related to autograft bone harvest. Compare this to a self-administered questionnaire of autograft patients, in which 32% still experience pain at the donor site two years after surgery.

Infuse Bone Graft eliminates hip pain and complications related to autograft bone harvest.

Economic Impact1,2

The percentage of patients working before and after the surgery was part of the study. The results indicated the work status of the investigational patients was higher, although statistically equivalent, than that of the control patients at all postoperative follow-up intervals.

From a hospital perspective, approximately 50% of the incremental costs of the recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) utilization are offset by the cost savings associated with eliminating the iliac crest harvesting procedure:

  • Operating room time is reduced by approximately 30 minutes and using a conservatively estimated cost of $18/min, the result is a $540 offset.
  • A statistically significant decrease was realized in blood loss among Infuse Bone Graft patients.

Autograft Infuse Bone Graft

Operative Time

2.0

1.6

Blood Loss (ml)

153.1

109.8

Hospital Stay (days)

3.3

3.1

  Statistically significant difference relative to control population

PRECLINICAL STUDIES

The preclinical studies examined spinal fusion in animals facilitated by recombinant human bone morphogenetic protein-2 (rhBMP-2), both in achieving fusion and in determining the appropriate amount of the protein.

Lower-Order Animal Study6, 7*

The objective of this study was to compare the effectiveness of a single titanium cylindrical cage filled with either autograft from the iliac crest or rhBMP-2/absorbable collagen sponge (ACS) in the sheep lumbar spine after six months. The results were:

  • Plain film radiographs suggest 100% fusion rate in both groups.
  • Histological findings revealed a 37% fusion rate for autograft compared to 100% for rhBMP-2/ACS.
  • The autograft group demonstrated a 16-fold greater area of fibrous tissue in the sagittal sections compared with the rhBMP-2 group (p<0.01).

The study produced this conclusion:

  • Histology is the most definitive method of determining whether a solid fusion has occurred.
  • Plain film radiograph appears to overestimate fusion success with autograft.
Study suggests histology is the most definitive method of determining solid fusion rates.
Histological evaluation demonstrates better fusion with rhBMP-2 compared to iliac crest autograft.

Higher-Order Animal Study8

This preclinical study was designed to find the appropriate concentration of rhBMP-2. The model focused on single-level interbody fusion in a rhesus monkey, and the study lasted six months.

The study groups included: (n)

Titanium cylindrical cage + Buffer

2

Titanium cylindrical cage + 0.75 mg/cc rhBMP-2/ACS

2

Titanium cylindrical cage + 1.50 mg/cc rhBMP-2/ACS

3

The results were:

  • Buffer/ACS demonstrated 0% fusion.
  • Both rhBMP-2/ACS groups demonstrated 100% fusion effectiveness.
  • 1.50mg/cc concentration had faster and denser bone formation compared to 0.75mg/cc.
  • Other carriers may require different rhBMP-2 concentration.

*

Animal studies are not necessarily indicative of human clinical outcome.


1

Burkus JK, Gornet MF, Dickman C, Zdeblick TA. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech. 2002;15(5):337-349.

2

Polly DW, Ogilvie JW, Mafilios MS, Ackerman SJ, Wang JC, Helm SE, Shaffrey CI, Stralka SW, Sahdhu HS. A cost analysis of bone morphogenetic protein versus autogenous iliac crest bone graft in a single-level anterior lumbar fusion. Orthopedics. 2003;26(10):1027-1037.

3

Simmonds MC, Brown JV, Heirs MK, Higgins JP, Mannion RJ, Rodgers MA, Stewart LA. Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data. Ann Intern Med. 2013 Jun 18;158(12):877-89.

4

Fu R, Selph S, McDonagh M, Peterson K, Tiwari A, Chou R, Helfand M. Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis. Ann Intern Med. 2013 Jun 18;158(12):890-902.

5

Please refer to the Yale University Open Data Access (YODA) Project website for the specific details around the data management program.

6

McKay B, Sandhu HS. Use of recombinant human bone morphogenetic protein-2 in spinal fusion applications. Spine (Phila Pa 1976). 2002 Aug.

7

McKay WF, Peckham SM, Marotta JS. The Science of rhBMP-2. St. Louis, MO: Quality Medical Publishing, Inc.: 2006.

8

Boden SD, Martin GJ Jr, Horton WC, Truss TL, Sandhu HS. Laparoscopic anterior spinal arthrodesis with rhBMP-2 in a titanium interbody threaded cage. J Spinal Disord Tech. 1998;11(2);95-101.


SPINAL INDICATIONS

BRIEF SUMMARY OF INDICATIONS, CONTRAINDICATIONS, AND WARNINGS FOR:
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
Infuse™ Bone Graft/Perimeter™ Interbody Fusion Device
Infuse™ Bone Graft/Clydesdale™ Spinal System
Infuse™ Bone Graft/Divergence-L™ Anterior/Oblique Lumbar Fusion System
Infuse™ Bone Graft/Pivox™ Oblique Lateral Spinal System

The Infuse™ Bone Graft/Medtronic Interbody Fusion Device is indicated for spinal fusion procedures in skeletally mature patients with degenerative disc disease (DDD) at one level from L2-S1, who may also have up to Grade I spondylolisthesis or Grade 1 retrolisthesis at the involved level.

The following interbody devices and surgical approaches may be used with Infuse™ Bone Graft:

  • The LT-Cage™ Lumbar Tapered Fusion Device, implanted via an anterior open or an anterior laparoscopic approach at a single level.
  • The Inter Fix™ or Inter Fix™ RP Threaded Fusion Device, implanted via an anterior open approach at a single level.
  • The Perimeter™ Interbody Fusion Device implanted via a retroperitoneal anterior lumbar interbody fusion (ALIF) at a single level from L2-S1 or an oblique lateral interbody fusion (OLIF) approach at a single level from L5-S1.
  • The Clydesdale™ Spinal System, implanted via an OLIF approach at a single level from L2-L5.
  • The Divergence-L™ Anterior/Oblique Lumbar Fusion System interbody device implanted via an ALIF approach at a single level from L2-S1 or an OLIF approach at a single level from L5-S1.
  • The Pivox™ Oblique Lateral Spinal System implanted via an OLIF approach at a single-level from L2-L5.

The Infuse™ Bone Graft/Medtronic Interbody Fusion Device consists of two components containing three parts – a spinal fusion cage, a recombinant human bone morphogenetic protein, and a carrier/scaffold for the bone morphogenetic protein and resulting bone. These components must be used as a system for the prescribed indication described above. 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 Interbody Fusion Device 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. The LT-Cage™ Lumbar Tapered Fusion Device, the Perimeter™ Interbody Fusion Device, the Clydesdale™ Spinal System, the Divergence-L™ Anterior/Oblique Lumbar Fusion System, and the Pivox™ Oblique Lateral Spinal System implants are not to be used in conjunction with either the Inter Fix™ OR Inter Fix™ RP implants to treat a spinal level.

The Infuse™ Bone Graft/Medtronic 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 and 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; in patients who are skeletally immature; in pregnant women; or in patients with an active infection at the operative site or with an allergy to titanium, titanium alloy, or polyetheretherketone (PEEK).

There are no adequate and well-controlled studies in human pregnant women. In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are capable of crossing the placenta. Women of child bearing potential should be warned by their surgeon of potential risk to a fetus and informed of other possible orthopedic treatments. The safety and effectiveness of this device has not been established in nursing mothers. Women of child- bearing potential should be advised to not become pregnant for one year following treatment with this device.

Please see the Infuse™ Bone Graft package insert for the complete list of indications, warnings, precautions, adverse events, clinical results, definition of DDD, and other important medical information. The package insert also matches the sizes of those sized devices that are indicated for use with the appropriate Infuse™ Bone Graft kit. An electronic version of the package insert may be found at www.medtronic.com/manuals.

CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician with appropriate training or experience.

TIBIA TRAUMA INDICATIONS

BRIEF SUMMARY OF INDICATIONS, CONTRAINDICATIONS, AND WARNINGS FOR:
INFUSE™ BONE GRAFT

Infuse Bone Graft is indicated for treating acute, open tibial shaft fractures that have been stabilized with IM nail fixation after appropriate wound management. Infuse Bone Graft must be applied within 14 days after the initial fracture. Prospective patients should be skeletally mature.

Infuse Bone Graft consists of two components – recombinant human Bone Morphogenetic Protein-2 solution and a carrier/scaffold for the bone morphogenetic protein solution and resulting bone. These components must be used as a system. 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.

Infuse Bone Graft 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 and should not be used in the vicinity of a resected or extant tumor, in patients with an active malignancy or patients undergoing treatment for a malignancy. Infuse Bone Graft should also not be used in patients who are skeletally immature, in patients with an inadequate neurovascular status, in patients with compartment syndrome of the affected limb, in pregnant women, or in patients with an active infection at the operative site.

There are no adequate and well controlled studies in human pregnant women. In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are capable of crossing the placenta. Women of child bearing potential should be warned by their surgeon of potential risk to a fetus and informed of other possible orthopedic treatments. The safety and effectiveness of this device has not been established in nursing mothers. Women of child-bearing potential should be advised to not become pregnant for one year following treatment with this device.

Please see the package insert for the complete list of indications, warnings, precautions, adverse events, clinical results, and other important medical information.

CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician with appropriate training or experience.

ORAL MAXILLIOFACIAL INDICATIONS

BRIEF SUMMARY OF INDICATIONS, CONTRAINDICATIONS, WARNINGS, AND PRECAUTION FOR INFUSE™ BONE GRAFT FOR CERTAIN ORAL MAXILLOFACIAL AND DENTAL REGENERATIVE USES

Infuse Bone Graft is indicated as an alternative to autogenous bone graft for sinus augmentations, and for localized alveolar ridge augmentations for defects associated with extraction sockets.

The Infuse Bone Graft consists of two components – recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) placed on an absorbable collagen sponge (ACS). These components must be used as a system for the prescribed indication. 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 the package insert.

Infuse Bone Graft 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 and 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, in pregnant women, or patients with an active infection at the operative site.

There are no adequate and well-controlled studies in human pregnant women. In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are capable of crossing the placenta. Women of child bearing potential should be warned by their surgeon of potential risk to a fetus and informed of other possible dental treatments. The safety and effectiveness of this device has not been established in nursing mothers. Women of child-bearing potential should be advised to not become pregnant for one year following treatment with this device.

Infuse Bone Graft has not been studied in patients who are skeletally immature (<18 years of age or no radiographic evidence of epiphyseal closure).

Please see the package insert for the complete list of indications, warnings, precautions, adverse events, clinical results, and other important medical information.