Tibial Delayed Healing Pivotal Clinical Trial

Official Title: “A Prospective, Randomized, Multicenter Pivotal Clinical Trial of the INFUSE/MASTERGRAFT™ Delayed Healing Device With Rigid Internal Fixation in the Treatment of Tibial Delayed Healing”

Evaluate the INFUSE/MASTERGRAFT™ Delayed Healing Device as an alternative/replacement to autograft in the treatment of tibial delayed healing.

The purpose of this study is to evaluate the INFUSE/MASTERGRAFT™ Delayed Healing Device as an alternative/replacement to autograft in the treatment of tibial delayed healing. A subject will be considered to have tibial delayed healing when he/she is at least six months from the date of the most recent surgical intervention and has shown no signs of radiographic healing for at least three months. Radiographic signs of healing for this study are defined as either the progressive disappearance of fracture lines or the development of cortical continuity [bridging bone] at the site. All prospective patients must require surgical treatment with rigid internal fixation [reamed IM nail or plate/screws] and bone grafting.

Intervention(s) in this Clinical Trial

• Device: Open implantation of INFUSE Bone Graft (rh BMP-2)
  • Protein-2 (rhBMP-2)) and absorbable collagen sponge (ACS) carrier at 1.50 mg/cc and MASTERGRAFT granules (biphasic ceramic) with appropriate rigid internal fixation hardware (reamed IM nail or plate/screws)
• Procedure: Open implantation of ICBG
  • and the appropriate rigid internal fixation hardware (reamed IM nail or plate/screws)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: INFUSE/MASTERGRAFT - Rigid Fixation
• Active Comparator: Autograft bone - Rigid internal fixation

Primary Measures

• Overall success
  • Time Frame: 12 Months
    Safety Issue?: No

Secondary Measures

• SF-36 Health Survey
  • Time Frame: 12 months
    Safety Issue?: No
• Short Musculoskeletal Functional Assessment (SMFA)
  • Time Frame: 12 months
    Safety Issue?: No
• Radiographic union (a component of overall success)
  • Time Frame: 12 months
    Safety Issue?: No
• Success in weight bearing ability (a component of overall success)
  • Time Frame: 12 months
    Safety Issue?: No
• Improvement in pain at the delayed healing site (a component of overall success)
  • Time Frame: 12 months
    Safety Issue?: No
• No serious adverse event classified as "implant associated" or "implant/surgical procedure associated;" (a component of overall success)
  • Time Frame: 12 months
    Safety Issue?: Yes
• No additional surgical procedure classified as a "failure." (a component of overall success)
  • Time Frame: 12 months
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Has tibial delayed healing. A subject will be considered to have delayed healing when he/she is at least six months from the date of the most recent surgical intervention and has shown no signs of radiographic healing for at least three months. (Radiographic signs of healing for this study are defined as either the progressive disappearance of fracture lines or the development of cortical continuity
• [bridging bone] at the site.)
• 2. Has delayed healing of the tibia that requires treatment with rigid internal fixation and bone grafting. (Stable rigid internal fixation hardware may already be in place prior to treatment. If required, the fixation hardware may be removed and replaced along with the placement of the bone graft.)
• 3. Has adequate soft tissue coverage at the delayed healing site. All prior soft tissue coverage procedures (e.g., skin grafts or flaps) should be sufficiently healed for placement of a bone graft prior to enrollment in the study.
• 4. Has a sufficient amount of iliac crest autograft available for a bone grafting procedure.
• 5. After walking 5 or 6 steps, has intensity of pain/discomfort at the injury site equal to or greater than 4 (as reported on the preoperative Delayed Healing Site Pain Questionnaire form; 0 being no pain and 10 being pain as bad as it could be).
• 6. Is at least 21 years of age and skeletally mature at the time of surgery.
• 7. If a female of child-bearing potential, patient is not pregnant or nursing and agrees not to become pregnant for one year following surgery in the study.
• 8. Is willing and able to comply with the study plan and able to understand and sign the Patient Informed Consent Form.

Exclusion Criteria:

• 1. Has a congenital pseudarthrosis or pathological fracture nonunion (not including osteoporosis-related fractures).
• 2. Has a tibial delayed healing with articular involvement (e.g., intra-articular).
• (The original fracture may have involved the joint, but the resulting delayed healing site may not involve the joint.)
• 3. Has hypertrophic tibial delayed healing (e.g., observed on x-ray as having an abundant callus or "horse hoof" appearance).
• 4. Has inadequate neurovascular status in the involved limb that may jeopardize healing.
• 5. Has an active or a known prior infection at the delayed healing site (e.g., the presence of purulent drainage from the site, prior positive cultures from the site, or evidence of active/prior osteomyelitis at the site). Enrolled subjects whose intra-operative cultures test positive for bacteria may remain in the study.
• 6. Has existing stable hardware that will not be removed and does not meet the algorithm requirements.
• 7. Has treatment planned for the delayed healing that does NOT include placement of a bone graft and/or rigid internal fixation consisting of a reamed intramedullary nail or plate/screws.
• 8. Has a tibial delayed healing injury site with a bony defect larger than 4 cm in length.
• 9. Has another injury/condition that prevents ambulation or completion of any of the study assessments.
• 10. Has a history of endocrine or metabolic disorder known to affect osteogenesis (e.g., Paget's disease, renal osteodystrophy, hyperthyroidism, parathyroid hormone disorder, Ehler-Danlos syndrome, osteogenesis imperfecta, calcium imbalance).
• 11. Has a Vitamin D deficiency, defined as a 25-hydroxy Vitamin D serum concentration of ≤11ng/mL .
• 12. Has an active malignancy or prior history of malignancy (except for basal cell carcinoma of the skin).
• 13. Has an overt or active systemic infection (e.g., HIV/AIDS, hepatitis, bacteremia).
• 14. Has been on oral or injectable steroids for six weeks or more at time of enrollment.
• This does not include episodic steroid use; inhaled steroids; or steroid medication (e.g., Epidural Steroid Injections, Medrol DosePaks) specifically for the perioperative management of symptoms.
• 15. Has a condition requiring postoperative medications that could interfere with bone healing of the implant, such as steroids. This does not include low dose aspirin for prophylactic anticoagulation; routine perioperative anti-inflammatory drugs; episodic steroid use; or inhaled steroids.
• 16. Has a history of certain autoimmune diseases. (Refer to the List of Autoimmune
• Diseases in the CIP for further information.)
• 17. Has a history of exposure to injectable collagen or silicone implants.
• 18. Has any previous exposure to any recombinant BMPs of either human or animal extraction.
• 19. Has a history of hypersensitivity to collagen or protein pharmaceuticals (e.g., monoclonal antibodies or gamma globulins).
• 20. Has a history of allergy to bovine collagen products.
• 21. Has a documented allergy or intolerance to metal or metal alloys, such as stainless steel or titanium.
• 22. Has chronic or acute renal and/or hepatic failure or prior history of renal and/or hepatic parenchymal disease.
• 23. Is mentally incompetent. If questionable, obtain psychiatric consult.
• 24. Is a prisoner.
• 25. Is an alcohol and/or drug abuser as defined by currently undergoing treatment for alcohol and/or drug abuse.
• 26. Has received treatment with an investigational therapy (drug, device, and/or biologic) within 28 days prior to implantation surgery or such treatment is planned during the 12-month period following the study surgery

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Medtronic Spinal and Biologics Industry

Overall Clinical Trial Officials and Contacts

Overall Contact: Clinical Department (800)-876-3133 msbkclinicalresearch@medtronic.com

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01016067

Study ID Number: Medtronic P07-01

ClinicalTrials.gov Identifier: NCT01016067

Health Authority: United States: Food and Drug Administration