Tibial FracturesPhase 4NCT00853489
rhBMP-2 Versus Autograft in Critical Size Tibial Defects
A Phase 4 study testing recombinant bone morphogenetic protein 2 and Autogenous iliac crest bone graft in people with Tibial Fractures, run by St. Louis University at 13 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tibial Fractures
- What is being tested?
- recombinant bone morphogenetic protein 2 and Autogenous iliac crest bone graft
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 13 sitesUnited States
- Study dates
- Aug 2011to 17 Feb 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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?
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Boston Medical Center
Boston, Massachusetts, 02118
Carolinas Medical Center
Charlotte, North Carolina, 28232
MetroHealth Medical Center
Cleveland, Ohio, 44109
Denver Health and Hospital Authority
Denver, Colorado, 80204
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234-6315
University of Iowa Hospitals
Iowa City, Iowa, 52242
Hennepin County Medical Center
Minneapolis, Minnesota, 55715
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
University of Oklahoma / OU Medical Center
Oklahoma City, Oklahoma, 73104
UCSF Medical Center
San Francisco, California, 94115
University of Washington / Harborview Medical Center
Seattle, Washington, 98104-2499
St. Louis Medical Center
St Louis, Missouri, 63110
Florida Orthopaedic Institute / Tampa General & St. Joseph's Hospitals
Tampa, Florida, 33606
About this study
Official title: 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).
Read the 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.
- Conditions
- Tibial Fractures
- Being tested
- recombinant bone morphogenetic protein 2, Autogenous iliac crest bone graft
- Keywords
- Open tibia fractures, rhBMP-2, critical size defects, bone grafting
- Medical subject headings
- Tibial Fractures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant bone morphogenetic protein 2Device
Also called (rhBMP-2) (INFUSE)
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
Autogenous iliac crest bone graftProcedure or surgery
Patients will undergo autogenous iliac crest bone graft surgery per the surgeon's usual practice.
| Study group | Role | What they receive |
|---|---|---|
| recombinant bone morphogenetic protein 2 | Experimental | The patient will receive rhBMP-2 plus allograft chips in the bone defect site. Intervention type: surgical Receives: Device: recombinant bone morphogenetic protein 2 |
| Autogenous iliac crest bone graft | Active comparator | Bone will be harvested from the iliac crest and placed in the bone defect. Receives: Procedure: Autogenous iliac crest bone graft |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fracture Healing (Union) at 12 Months
Union will be defined by:
- Radiographic union as defined by the Radiographic union scale in tibia fractures (RUST) score, Radiographic evaluation will be assessed by blinded orthopaedic surgeons.
Measured: 12 months post op
Secondary outcomes (2)
Infection
Infection will be assessed based on the CDC criteria for deep and superficial infection.
Measured: 12 months post op.
Medical Cost
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.
Measured: 12 mos post op
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2009 (estimated)
- Study startAug 2011
- Primary completion17 Feb 2017
- Study completion17 Feb 2017
Why it stopped: Enrollment too slow
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tibial FracturesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Louis University
- Sponsor type
- University, hospital or other
- Collaborators
- Major Extremity Trauma Research Consortium
- Responsible party
- Principal investigator, Thomas Revak, DO, St. Louis University
- Investigators
- Thomas Revak, DO, Principal investigator, St. Louis Medical CenterPaul Tornetta, MD, Principal investigator, Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00853489
- Sponsor's protocol ID
- W81XWH-09-20108
- Other IDs
- 15915
- Status last verified
- Oct 2018
- First submitted
- 24 Feb 2009
- Last updated
- 25 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RhBMP-2 vs. Autograft for Critical Size Tibial Defects: A Multicenter Randomized Trial
- ClinicalTrials.gov ID
- NCT00853489
- Acronym / sponsor ID
- W81XWH-09-20108
- Conditions
- Tibial Fractures
- Keywords
- Open tibia fractures, rhBMP-2, critical size defects, bone grafting
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment too slow
- Enrolment
- 33 participants (actual)
- Lead sponsor
- St. Louis UniversityUniversity, hospital or other
- Collaborators
- Major Extremity Trauma Research Consortium
- Study start
- Aug 2011
- Primary completion
- 17 Feb 2017 (actual)
- Study completion
- 17 Feb 2017 (actual)
- First posted
- 2 Mar 2009 (estimated)
- Results
- Posted 13 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| recombinant bone morphogenetic protein 2 | Experimental | Device: recombinant bone morphogenetic protein 2The patient will receive rhBMP-2 plus allograft chips in the bone defect site. Intervention type: surgical |
| Autogenous iliac crest bone graft | Active comparator | Procedure: Autogenous iliac crest bone graftBone will be harvested from the iliac crest and placed in the bone defect. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant bone morphogenetic protein 2Also: (rhBMP-2) (INFUSE)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 | Device | recombinant bone morphogenetic protein 2 |
| Autogenous iliac crest bone graftPatients will undergo autogenous iliac crest bone graft surgery per the surgeon's usual practice. | Procedure or surgery | Autogenous iliac crest bone graft |
Primary outcome
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.
2 secondary outcomes
Infection
Time frame: 12 months post op.
Medical Cost
Time frame: 12 mos post op
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Revak, DO principal investigator
St. Louis Medical Center
Paul Tornetta, MD principal investigator
Boston Medical Center
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing recombinant bone morphogenetic protein 2 and Autogenous iliac crest bone graft in people with Tibial Fractures, run by St. Louis University at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fracture Healing (Union) at 12 Months (time frame: 12 months post op). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2018.