rhBMP-2 Versus Autograft in Critical Size Tibial Defects

Open tibia fractures have a 15% or higher rate of not healing. Those fractures which do not
heal are typically treated with bone from the hip (iliac crest autograft; or ICBG). The use
of ICBG bone with the treatment of delayed unions/non-unions with critical defect, although
successful, has its drawbacks. The bone graft sources are limited and the procedure is
associated with additional operating room time plus a second incision with increased risk of
infection, post operative pain and increased hospital stay. The purpose of this study is to
determine if Rh-BMP2, a new bone graft substitute, is at least as effective as using bone
from the hip (autograft) to help promote healing of open, tibia (shin bone) fractures.

Research Questions:

Primary:

What is the relative effect of rhBMP-2 versus autogenous ICBG on rates of union in patients
with critical size defects following tibial shaft fractures?

Null hypothesis #1: rhBMP-2 has the same union rate when used in critical-sized defects as
does ICBG.

Secondary:

What is the relative effect of rhBMP-2 versus autogenous ICBG on infection rates in patients
with nonunion or critical size defects following tibial shaft fractures?

Null hypothesis #2: The infection rate in open tibias with critical-sized defects treated
with rhBMP-2 and autogenous ICBG are the same.

What is the economic impact of the use of Rh-BMP 2 for tibial fractures with critical sized
defects?

Null hypothesis #3: There will be no difference in the economic cost of the treatment of
critical sized defects using the RhBMP-2 versus iliac crest bone graft.

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?