Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

rhBMP-2 Versus Autograft in Critical Size Tibial Defects

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.
 
ClinicalTrials.gov Identifier: NCT00853489
Recruitment Status : Terminated (Enrollment too slow)
First Posted : March 2, 2009
Results First Posted : March 13, 2018
Last Update Posted : October 25, 2018
Sponsor:
Collaborator:
Major Extremity Trauma Research Consortium
Information provided by (Responsible Party):
Thomas Revak, DO, St. Louis University

Tracking Information
First Submitted Date  ICMJE February 24, 2009
First Posted Date  ICMJE March 2, 2009
Results First Submitted Date  ICMJE February 14, 2018
Results First Posted Date  ICMJE March 13, 2018
Last Update Posted Date October 25, 2018
Study Start Date  ICMJE August 2011
Actual Primary Completion Date February 17, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2018)
Fracture Healing (Union) at 12 Months [ Time Frame: 12 months post op ]
Union will be defined by: 1. Radiographic union as defined by the Radiographic union scale in tibia fractures (RUST) score, Radiographic evaluation will be assessed by blinded orthopaedic surgeons.
Original Primary Outcome Measures  ICMJE
 (submitted: February 27, 2009)
Fracture Healing (Union) at 12 Months [ Time Frame: 12 months post op ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2018)
  • Infection [ Time Frame: 12 months post op. ]
    Infection will be assessed based on the CDC criteria for deep and superficial infection.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2009)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE rhBMP-2 Versus Autograft in Critical Size Tibial Defects
Official Title  ICMJE RhBMP-2 vs. Autograft for Critical Size Tibial Defects: A Multicenter Randomized Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Tibial Fractures
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 10, 2017)
33
Original Estimated Enrollment  ICMJE
 (submitted: February 27, 2009)
50
Actual Study Completion Date  ICMJE February 17, 2017
Actual Primary Completion Date February 17, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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?
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00853489
Other Study ID Numbers  ICMJE W81XWH-09-20108
15915 ( Other Identifier: Saint Louis University Institutional Review Board )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Revak, DO, St. Louis University
Study Sponsor  ICMJE St. Louis University
Collaborators  ICMJE Major Extremity Trauma Research Consortium
Investigators  ICMJE
Principal Investigator: Thomas Revak, DO St. Louis Medical Center
Principal Investigator: Paul Tornetta, MD Boston Medical Center
PRS Account St. Louis University
Verification Date October 2018

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