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rhBMP-2 Versus Autograft in Critical Size Tibial Defects

This study has been terminated.
(Enrollment too slow)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00853489
First Posted: March 2, 2009
Last Update Posted: November 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Major Extremity Trauma Research Consortium
Information provided by (Responsible Party):
St. Louis University
February 24, 2009
March 2, 2009
November 10, 2017
August 2011
February 17, 2017   (Final data collection date for primary outcome measure)
Fracture healing (union) at 12 months [ Time Frame: op2 weeks, 6 weeks, 12 weeks, 18 weeks, 6 months and 12 months post op ]

Union will be defined by meeting both of the following criteria:

  1. Radiographic union as defined by the RUST score, Radiographic evaluation will be assessed by blinded orthopaedic surgeons.
  2. Clinical union as defined by pain-free full weight bearing and lack of tenderness ,swelling and pain at the fracture site on palpation. Pain will be documented using the VAS at each visit. Swelling will be defined as the absence of skin wrinkling.
Fracture healing (union) at 12 months [ Time Frame: 12 months post op ]
Complete list of historical versions of study NCT00853489 on ClinicalTrials.gov Archive Site
  • Infection [ Time Frame: 2 weeks, 6 weeks, 12 weeks, 18 weeks, 6 months and 12 months post op. ]
    Infection will be assessed based on the CDC criteria for deep and superficial infection.
  • Functional Status [ Time Frame: 2 weeks, 6 weeks, 12 weeks, 18 weeks, 6 months and 12 months post op ]
    Function will be measured using the SF12 and the Short Form Musculoskeletal Assessment (SMFA)
  • Medical Cost [ Time Frame: 12 mos post op ]
    An economic evaluation will also be performed including the costs of iliac crest bone graft harvest and complications from the bone graft surgery and the cost of the Rh-BMP 2 and the biologic implant used in the treatment group.
  • Wound healing and infection [ Time Frame: The patients in both groups will be evaluated at 2 weeks, 6 weeks, 12 weeks, 18 weeks, 6 months and 12 months ]
  • Cost-effectiveness evaluation [ Time Frame: 12 months post op ]
Not Provided
Not Provided
 
rhBMP-2 Versus Autograft in Critical Size Tibial Defects
RhBMP-2 vs. Autograft for Critical Size Tibial Defects: A Multicenter Randomized Trial
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).

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.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Tibial Fractures
  • Device: recombinant bone morphogenetic protein 2
    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
    Other Name: (rhBMP-2) (INFUSE)
  • Procedure: Autogenous iliac crest bone graft
    Patients will undergo autogenous iliac crest bone graft surgery per the surgeon's usual practice.
  • Experimental: recombinant bone morphogenetic protein 2
    The patient will receive rhBMP-2 plus allograft chips in the bone defect site. Intervention type: surgical
    Intervention: Device: recombinant bone morphogenetic protein 2
  • Active Comparator: Autogenous iliac crest bone graft
    Bone will be harvested from the iliac crest and placed in the bone defect.
    Intervention: Procedure: Autogenous iliac crest bone graft
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
33
February 17, 2017
February 17, 2017   (Final data collection date for primary outcome measure)

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?
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00853489
W81XWH-09-20108
15915 ( Other Identifier: Saint Louis University Institutional Review Board )
Yes
Not Provided
Not Provided
St. Louis University
St. Louis University
Major Extremity Trauma Research Consortium
Principal Investigator: Lisa Cannada, MD St. Louis Medical Center
Principal Investigator: Paul Tornetta, MD Boston Medical Center
St. Louis University
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP