rhBMP-2 Versus Autograft in Critical Size Tibial Defects
Condition: Tibial Fractures
MeSH terms: Tibial Fractures
Intervention: recombinant bone morphogenetic protein 2; Autogenous iliac crest bone graft
Intervention description: Patients will receive 1.50 mg/ml -12 mg of rhBMP-2 soaked on a absorbable collagen sponge (rhBMP-2/ACS) as an adjuvant to a freeze-dried cancellous allograft; Patients will undergo autogenous iliac crest bone graft surgery per the surgeon's usual practice.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Open tibia fractures; rhBMP-2; critical size defects; bone grafting

Summary:

      The purpose of our study is to evaluate the use of recombinant human bone morphogenetic
      protein 2 (RhBMP-2) as compared to standard ICBG in the treatment of severe open tibia
      fractures with a critical size bone defect (at least one centimeter in length compromising at
      least 50% of the circumference of the bone).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients 18-65 years old with an open tibia fracture involving diaphysis (if patient
             has a bilateral tibia fracture and both require a bone graft, then each will be
             randomized separately).

          -  Tibia fractures with a circumferential bone defect of at least one centimeter in
             length compromising at least 50% of the circumference of the bone.

          -  The definitive treatment of the tibia fracture must be with an intramedullary nail
             (may have temporary external fixation prior to IM nail placement).

          -  Patients whose treatment plan includes placement of a bone graft between 6 to 16 weeks
             after their initial injury.

          -  Patients who have no evidence of infection by clinical examination (defined as active
             infection at the operative site, purulent drainage from the fracture or evidence of
             active osteomyelitis at the time of bone graft).

          -  Patients who are independent in living and ambulation prior to injury.

          -  Patients who are English speaking.

          -  Patients who are willing to provide consent and available for follow-up for at least
             12 months following definitive surgical procedure.

        Exclusion Criteria:

          -  Patients who are pregnant or lactating.

          -  Patients with known hypersensitivity to rhBMP-2 or bovine type I collagen.

          -  Patients with a history of tumor, a resected or extant tumor, an active malignancy, or
             patients undergoing treatment for malignancy.

          -  Patients who are skeletally immature (<18 years of age or no radiographic evidence of
             epiphyseal closure).

          -  Patients with inadequate neurovascular status, e.g. high risk of amputation.

          -  Patients with compartment syndrome of the affected limb.

          -  Patients with immune deficiency or history of auto-immune disease,

          -  Patients who have undergone treatment of any other investigational therapy within the
             month preceding implantation or planned within the 12 months following implantation.

          -  Patients unable to return for required follow-up visits.

          -  Patients who have medical co-morbidities that preclude treatment with a general
             anesthetic.

          -  Patient who is pending incarceration or who is incarcerated.

          -  Patients with an active infection at the operative site, purulent drainage from the
             fracture or evidence of active osteomyelitis at the time of bone grafting.

          -  Patient has intraoperative positive gram stain or an elevated CRP after laboratory
             screening for infection.

          -  Patient has segmental defects longer than 5cm in length.

          -  Patients who have segmental defects that require more than 60 cc of bone graft.

          -  Patients who require more than one large kit of rhBMP-2 at time of surgery.

          -  Patient's anticipated treatment plan also includes the use of other procedures to
             promote fracture healing, e.g. ultrasound, magnetic field or electrical stimulation.

          -  Patient's tibia fracture has been treated with additional fixation beyond the
             intramedullary nail, e.g. plates, wires or screws.

          -  Patients who have pathological fractures; a known history of Paget's disease or known
             history of heterotropic calcification.

          -  Patients with a Glasgow Coma Scale less than 15 (less than fully awake) at the time of
             informed consent.

          -  Patients with previous hardware in place that prevents placement of an intramedullary
             nail for treatment of the tibial shaft fracture.

          -  Patients with prior use of INFUSE.

        If the patient is a female of child bearing potential:

          -  Does she have a negative pregnancy test (administered within 72 hours prior to
             surgery)?

          -  Has she agreed to use adequate contraception for a period of at least 1 year following
             implementation of rhBMP-2?