Tibial Delayed Healing Pivotal Clinical Trial
Condition: Tibial Delayed Healing
Intervention: INFUSE/MASTERGRAFT; Autograft bone
Intervention description: INFUSE® (rhBMP-2) on an absorbable collagen sponge (ACS) and MASTERGRAFT® granules with appropriate rigid internal fixation hardware (reamed IM nail or plate/screws); Autogenous bone graft with appropriate rigid internal fixation hardware (reamed IM nail or plate/screws)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Tibia; Tibial; Fracture; Nonunion; delayed; healing; iliac; crest; autograft; INFUSE; MASTERGRAFT; Fixation; Internal

Summary:

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

Eligibility criteria:

        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