Tibial Fractures
Conditions
Keywords
Open Diaphyseal Tibia Fractures
Brief summary
Demonstrate a larger proportion of subjects with healed fractures among subjects treated with InductOs and reamed, locked intramedullary nailing compared to subjects treated with reamed, locked intramedullary nailing alone.
Interventions
DRUGInductOs
InductOs is rhBMP-2/ACS 1.5 mg/ml implanted once at the time of definitive fracture coverage
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with acute open tibial shaft fractures (Gustilo Type I, II, IIIA, or IIIB) who require surgical management with reamed, statically locked intramedullary nail fixation and who are at low risk for amputation. * Subjects should be at least 18 years of age, be skeletally mature, and be able to provide written informed consent. * Initial fracture stabilization and wound debridement should occur within 1 day after injury and DFC should occur within 14 days after injury.
Exclusion criteria
* Planned treatment for the fracture should not include further procedures to promote fracture healing. After 16 weeks have elapsed since DFC, unanticipated procedures to promote fracture healing are permitted as clinically indicated. * Presence of fracture distraction \> 2 mm following definitive fracture fixation. * Presence of purulent drainage from the fracture site or evidence of active osteomyelitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Healed Fractures | 13 and 20 weeks | Patients categorized by investigator as healed, not healed, no outcome (using pre-specified criteria). Healed: no tenderness at fracture site or pain with weight bearing, presence of bridging callus or disappearance of fracture lines, no hardware failure, no secondary intervention to promote fracture healing. Not healed: diagnosis of delayed union or nonunion, hardware failure, secondary intervention procedure for fracture healing recommended or performed, or conduct of procedure that may interfere with fracture healing. No outcome: subjects who did not achieve either healed or not healed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieving Combined Clinical and Radiographic Endpoint (CCRE) | 1 year | Patients categorized as Success or Failure of CCRE. Success defined as a fracture judged to be both clinically healed by clinical investigator, healed (see primary outcome), and radiographically united by independent, blinded radiology panel, united. Patients deemed not healed or not united were assessed as failures. |
Countries
Belgium, Finland, France, Germany, Italy, Netherlands, Norway, Poland, Romania, South Africa, Spain, United Kingdom
Participant flow
Recruitment details
Patients were recruited worldwide from September 2003 to July 2007.
Pre-assignment details
Assessment of the fractured limb was performed 24 hours before surgical fixation. Patients were stratified by severity of fracture (using Gustilo-Anderson Classification).
Participants by arm
| Arm | Count |
|---|---|
| rhBMP-2/ACS InductOs (dibotermin alfa) contains 12 mg of recombinant human bone morphogenetic protein-2 (rhBMP-2) in the form of a 1.5 mg/ml solution on an absorbable collagen sponge (ACS) implanted once at the time of definitive fracture coverage + surgical fixation | 139 |
| Standard of Care Standard of Care: Surgical fixation only | 138 |
| Total | 277 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 17 | 13 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol deviation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | rhBMP-2/ACS | Standard of Care | Total |
|---|---|---|---|
| Age Continuous | 39.48 years STANDARD_DEVIATION 15.4 | 37.54 years STANDARD_DEVIATION 14.87 | 38.52 years STANDARD_DEVIATION 15.14 |
| Sex: Female, Male Female | 26 Participants | 27 Participants | 53 Participants |
| Sex: Female, Male Male | 113 Participants | 111 Participants | 224 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 127 / — | 123 / — |
| serious Total, serious adverse events | 31 / — | 25 / — |
Outcome results
Primary
Number of Patients With Healed Fractures
Patients categorized by investigator as healed, not healed, no outcome (using pre-specified criteria). Healed: no tenderness at fracture site or pain with weight bearing, presence of bridging callus or disappearance of fracture lines, no hardware failure, no secondary intervention to promote fracture healing. Not healed: diagnosis of delayed union or nonunion, hardware failure, secondary intervention procedure for fracture healing recommended or performed, or conduct of procedure that may interfere with fracture healing. No outcome: subjects who did not achieve either healed or not healed.
Time frame: 13 and 20 weeks
Population: All patients randomized were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhBMP-2/ACS | Number of Patients With Healed Fractures | Week 13 Healed | 83 patients |
| rhBMP-2/ACS | Number of Patients With Healed Fractures | Week 13 No outcome | 48 patients |
| rhBMP-2/ACS | Number of Patients With Healed Fractures | Week 20 Not healed | 29 patients |
| rhBMP-2/ACS | Number of Patients With Healed Fractures | Week 13 Not healed | 8 patients |
| rhBMP-2/ACS | Number of Patients With Healed Fractures | Week 20 No outcome | 15 patients |
| rhBMP-2/ACS | Number of Patients With Healed Fractures | Week 20 Healed | 95 patients |
| Standard of Care | Number of Patients With Healed Fractures | Week 20 No outcome | 18 patients |
| Standard of Care | Number of Patients With Healed Fractures | Week 20 Healed | 92 patients |
| Standard of Care | Number of Patients With Healed Fractures | Week 13 Healed | 66 patients |
| Standard of Care | Number of Patients With Healed Fractures | Week 13 Not healed | 13 patients |
| Standard of Care | Number of Patients With Healed Fractures | Week 13 No outcome | 59 patients |
| Standard of Care | Number of Patients With Healed Fractures | Week 20 Not healed | 28 patients |
Comparison: Comparison of Healed vs Not healed/No outcome for week 13.p-value: 0.0541Fisher Exact
Comparison: Comparison of Healed vs Not healed/No outcome for week 20.p-value: 0.7983Fisher Exact
Secondary
Number of Patients Achieving Combined Clinical and Radiographic Endpoint (CCRE)
Patients categorized as Success or Failure of CCRE. Success defined as a fracture judged to be both clinically healed by clinical investigator, healed (see primary outcome), and radiographically united by independent, blinded radiology panel, united. Patients deemed not healed or not united were assessed as failures.
Time frame: 1 year
Population: All patients randomized were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhBMP-2/ACS | Number of Patients Achieving Combined Clinical and Radiographic Endpoint (CCRE) | Success | 98 patients |
| rhBMP-2/ACS | Number of Patients Achieving Combined Clinical and Radiographic Endpoint (CCRE) | Failure | 41 patients |
| Standard of Care | Number of Patients Achieving Combined Clinical and Radiographic Endpoint (CCRE) | Success | 96 patients |
| Standard of Care | Number of Patients Achieving Combined Clinical and Radiographic Endpoint (CCRE) | Failure | 42 patients |
p-value: 0.8961Fisher Exact