Trial Outcomes & Findings for Study Evaluating InductOs in Diaphyseal Tibia Fractures (NCT NCT00161616)
NCT ID: NCT00161616
Last Updated: 2009-09-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
277 participants
Primary outcome timeframe
13 and 20 weeks
Results posted on
2009-09-07
Participant Flow
Patients were recruited worldwide from September 2003 to July 2007.
Assessment of the fractured limb was performed 24 hours before surgical fixation. Patients were stratified by severity of fracture (using Gustilo-Anderson Classification).
Participant milestones
| Measure |
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
|
Standard of Care
Standard of Care: Surgical fixation only
|
|---|---|---|
|
Overall Study
STARTED
|
139
|
138
|
|
Overall Study
COMPLETED
|
113
|
119
|
|
Overall Study
NOT COMPLETED
|
26
|
19
|
Reasons for withdrawal
| Measure |
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
|
Standard of Care
Standard of Care: Surgical fixation only
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
6
|
5
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
17
|
13
|
|
Overall Study
Protocol deviation
|
1
|
0
|
Baseline Characteristics
Study Evaluating InductOs in Diaphyseal Tibia Fractures
Baseline characteristics by cohort
| Measure |
rhBMP-2/ACS
n=139 Participants
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
|
Standard of Care
n=138 Participants
Standard of Care: Surgical fixation only
|
Total
n=277 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
39.48 years
STANDARD_DEVIATION 15.40 • n=5 Participants
|
37.54 years
STANDARD_DEVIATION 14.87 • n=7 Participants
|
38.52 years
STANDARD_DEVIATION 15.14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
113 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
224 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 13 and 20 weeksPopulation: All patients randomized were analyzed.
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.
Outcome measures
| Measure |
rhBMP-2/ACS
n=139 Participants
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
|
Standard of Care
n=138 Participants
Standard of Care: Surgical fixation only
|
|---|---|---|
|
Number of Patients With Healed Fractures
Week 20 Healed
|
95 patients
|
92 patients
|
|
Number of Patients With Healed Fractures
Week 13 Healed
|
83 patients
|
66 patients
|
|
Number of Patients With Healed Fractures
Week 13 Not healed
|
8 patients
|
13 patients
|
|
Number of Patients With Healed Fractures
Week 13 No outcome
|
48 patients
|
59 patients
|
|
Number of Patients With Healed Fractures
Week 20 Not healed
|
29 patients
|
28 patients
|
|
Number of Patients With Healed Fractures
Week 20 No outcome
|
15 patients
|
18 patients
|
SECONDARY outcome
Timeframe: 1 yearPopulation: All patients randomized were analyzed.
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.
Outcome measures
| Measure |
rhBMP-2/ACS
n=139 Participants
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
|
Standard of Care
n=138 Participants
Standard of Care: Surgical fixation only
|
|---|---|---|
|
Number of Patients Achieving Combined Clinical and Radiographic Endpoint (CCRE)
Failure
|
41 patients
|
42 patients
|
|
Number of Patients Achieving Combined Clinical and Radiographic Endpoint (CCRE)
Success
|
98 patients
|
96 patients
|
Adverse Events
rhBMP-2/ACS
Serious events: 31 serious events
Other events: 127 other events
Deaths: 0 deaths
Standard of Care
Serious events: 25 serious events
Other events: 123 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
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
|
Standard of Care
Standard of Care: Surgical fixation only
|
|---|---|---|
|
General disorders
Abcess
|
0.00%
0/139
|
0.72%
1/138
|
|
General disorders
Accidental injury
|
1.4%
2/139
|
2.9%
4/138
|
|
General disorders
Cellulitis
|
0.72%
1/139
|
0.00%
0/138
|
|
General disorders
Chest pain
|
0.72%
1/139
|
0.00%
0/138
|
|
General disorders
Fever
|
0.72%
1/139
|
0.00%
0/138
|
|
General disorders
Hardware failure
|
0.00%
0/139
|
1.4%
2/138
|
|
General disorders
Infection
|
10.8%
15/139
|
5.1%
7/138
|
|
General disorders
Pain
|
5.0%
7/139
|
1.4%
2/138
|
|
General disorders
Peritonitis
|
0.72%
1/139
|
0.00%
0/138
|
|
General disorders
Withdrawal syndrome
|
0.00%
0/139
|
0.72%
1/138
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/139
|
0.72%
1/138
|
|
Vascular disorders
Embolus
|
0.72%
1/139
|
0.00%
0/138
|
|
Vascular disorders
Pulmonary embolus
|
0.72%
1/139
|
0.00%
0/138
|
|
Cardiac disorders
Shock
|
0.00%
0/139
|
0.72%
1/138
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.4%
2/139
|
0.00%
0/138
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
Healing abnormal
|
0.00%
0/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
Healing abnormal: bleeding at wound site
|
0.00%
0/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
Healing abnormal: delayed wound healing
|
0.00%
0/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
Healing abnormal: drainage, oozing, discharge
|
0.72%
1/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
Healing abnormal: superficial wound breakdown
|
0.00%
0/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
Peripheral edema
|
0.72%
1/139
|
0.72%
1/138
|
|
Metabolism and nutrition disorders
SGPT increased
|
0.00%
0/139
|
0.72%
1/138
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.72%
1/139
|
0.00%
0/138
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/139
|
0.72%
1/138
|
|
Musculoskeletal and connective tissue disorders
Bone disorder
|
0.00%
0/139
|
0.72%
1/138
|
|
Musculoskeletal and connective tissue disorders
Bone fracture spontaneous
|
0.72%
1/139
|
0.00%
0/138
|
|
Musculoskeletal and connective tissue disorders
Fracture delayed union
|
1.4%
2/139
|
2.9%
4/138
|
|
Musculoskeletal and connective tissue disorders
Fracture malalignment
|
1.4%
2/139
|
2.2%
3/138
|
|
Musculoskeletal and connective tissue disorders
Fracture nonunion
|
0.00%
0/139
|
2.9%
4/138
|
|
Musculoskeletal and connective tissue disorders
Osteomyelitis
|
0.72%
1/139
|
0.00%
0/138
|
|
Nervous system disorders
Delirium
|
0.00%
0/139
|
0.72%
1/138
|
|
Nervous system disorders
Dizziness
|
0.00%
0/139
|
0.72%
1/138
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.72%
1/139
|
0.00%
0/138
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
0.72%
1/139
|
0.00%
0/138
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.72%
1/139
|
0.00%
0/138
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress syndrome
|
0.00%
0/139
|
0.72%
1/138
|
|
Skin and subcutaneous tissue disorders
Skin necrosis
|
0.00%
0/139
|
0.72%
1/138
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.72%
1/139
|
0.00%
0/138
|
|
Reproductive system and breast disorders
Prostatic carcinoma
|
0.72%
1/139
|
0.00%
0/138
|
Other adverse events
| Measure |
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
|
Standard of Care
Standard of Care: Surgical fixation only
|
|---|---|---|
|
General disorders
Fever
|
5.8%
8/139
|
5.8%
8/138
|
|
General disorders
Hardware failure
|
17.3%
24/139
|
14.5%
20/138
|
|
General disorders
Infection
|
20.1%
28/139
|
12.3%
17/138
|
|
General disorders
Lab test abnormal
|
9.4%
13/139
|
7.2%
10/138
|
|
General disorders
Pain
|
63.3%
88/139
|
60.9%
84/138
|
|
Blood and lymphatic system disorders
Anemia
|
23.7%
33/139
|
16.7%
23/138
|
|
Metabolism and nutrition disorders
Alkaline phosphatase increased
|
9.4%
13/139
|
9.4%
13/138
|
|
Metabolism and nutrition disorders
Amylase increased
|
7.2%
10/139
|
5.1%
7/138
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.2%
10/139
|
7.2%
10/138
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
7.9%
11/139
|
8.7%
12/138
|
|
Metabolism and nutrition disorders
Hypokalemia
|
4.3%
6/139
|
5.8%
8/138
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
4.3%
6/139
|
10.9%
15/138
|
|
Metabolism and nutrition disorders
Lactic dehydrogenase increased
|
19.4%
27/139
|
18.8%
26/138
|
|
General disorders
Peripheral edema
|
26.6%
37/139
|
29.0%
40/138
|
|
Metabolism and nutrition disorders
SGOT increased
|
17.3%
24/139
|
16.7%
23/138
|
|
Metabolism and nutrition disorders
SGPT increased
|
11.5%
16/139
|
9.4%
13/138
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.5%
16/139
|
5.1%
7/138
|
|
Musculoskeletal and connective tissue disorders
Fractured delayed union
|
7.2%
10/139
|
10.9%
15/138
|
|
Musculoskeletal and connective tissue disorders
Post operative heterotopic calcification
|
9.4%
13/139
|
5.8%
8/138
|
|
General disorders
Hypesthesia
|
7.9%
11/139
|
4.3%
6/138
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER