Clinical trial NCT00853489: rhBMP-2 Versus Autograft in Critical Size Tibial Defects
Official title: RhBMP-2 vs. Autograft for Critical Size Tibial Defects: A Multicenter Randomized Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Tibial Fractures
Keywords: Open tibia fractures
rhBMP-2
critical size defects
bone grafting
Lead sponsor: St. Louis University
Sponsor class: OTHER
Collaborators: name: Major Extremity Trauma Research Consortium
First posted: 2009-03-02
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

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?

Primary outcomes:
measure: Fracture Healing (Union) at 12 Months
timeFrame: 12 months post op
Secondary outcomes:
measure: Infection
timeFrame: 12 months post op.
measure: Medical Cost
timeFrame: 12 mos post op
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: Tampa
country: United States
facility: Florida Orthopaedic Institute / Tampa General & St. Joseph's Hospitals
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals
state: Iowa
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis Medical Center
state: Missouri
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma / OU Medical Center
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington / Harborview Medical Center
state: Washington
Study officials:
affiliation: St. Louis Medical Center
name: Thomas Revak, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Medical Center
name: Paul Tornetta, MD
role: PRINCIPAL_INVESTIGATOR
References: