Foot Fusion
Conditions
Keywords
arthritis, ankle pain, foot pain, hindfoot fracture, ankle fracture
Brief summary
STUDY OBJECTIVES: Demonstrate equivalent clinical and radiologic outcomes to the gold standard (ABG) in a representative clinical model (hindfoot and ankle fusions) STUDY HYPOTHESIS: Augment® Bone Graft is an equivalent bone grafting substitute to autologous bone graft in applications as shown by non-inferiority analysis STUDY RATIONALE: Evaluate a fully synthetic growth-factor enhanced bone graft substitute to facilitate fusion in conditions or injuries requiring bone graft in a representative clinical fusion model and thus the opportunity to provide equivalent union rates as ABG without necessitating an additional invasive procedure to harvest the graft REGULATORY PHASE: Investigational Device Exemption (IDE) for Premarket Approval (PMA) Application as a bone regeneration system, pivotal phase
Interventions
DEVICEAugment® Bone Graft
Augment® Bone Graft
PROCEDUREStandard of Care
Autologous Bone Graft
Sponsors
BioMimetic Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\) Bone defect in the hindfoot or ankle requiring fusion using open surgical technique with supplemental bone graft/substitute, requiring one of the following procedures: * Ankle joint fusion * Subtalar fusion * Calcaneocuboid fusion * Talonavicular fusion * Triple arthrodesis (subtalar, talonavicular and calcaneocuboid joints) * Double fusions (talonavicular and calcaneocuboid joints)
Exclusion criteria
1. Previous fusion surgery of the proposed fusion site. 2. The patient uses chronic medications known to affect the skeleton (e.g. glucocorticoid usage \> 10mg/day). 3. Pregnant or a female intending to become pregnant during this study period. 4. Morbidly obese (BMI \> 45 kg/m2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Fused at 24 Weeks (as Determined by CT Assessment) | 24 weeks | An independent radiologist examined CT images for all patients' joints and determined whether or not the joint had at least 50% osseous bridging. If a patient demonstrated all joints having at least 50% osseous bridging, this patient was classified as fused. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain on Weight Bearing | 24 and 52 Weeks | Subjects were asked to stand and report pain on a 100 mm Visual Analog Scale (with 0 being no pain and 100 being worst pain imaginable). 1. Clinically significant improvement: ≥20mm decrease from baseline 2. Detectable improvement: 10-20mm decrease from baseline 3. Maintained: \<10mm decrease from baseline and \<10mm increase from baseline 4. Deteriorated: \>10mm increase from baseline |
| Pain at Fusion Site | 24 and 52 weeks | Subjects were asked to report current pain level at the fusion site on a 100 mm Visual Analog Scale (with 0 being no pain and 100 being worst pain imaginable). 1. Clinically significant improvement: ≥20mm decrease from baseline 2. Detectable improvement: 10-20mm decrease from baseline 3. Maintained: \<10mm decrease from baseline and \<10mm increase from baseline 4. Deteriorated: \>10mm increase from baseline |
| Foot Function Index (FFI) | 24 and 52 weeks | The Foot Function Index (FFI) measures the impact of foot pathology on function in terms of pain, disability and activity restriction. The FFI is a self-administered index consisting of 23 items divided into 3 sub-scales. To obtain a sub-scale score, the item scores for a sub-scale are totaled and then divided by the maximum total possible for all of the sub-scale items which the subject indicated were applicable. Any item marked as not applicable is excluded from the total possible. Sub-scales are an average of the completed ratings within that sub-scale. The total foot function score is an average of the three sub-scale scores. Lower scores are indicative of better outcomes whereas higher scores indicate greater impairment. 1. Clinically significant improvement: ≥10 point decrease from baseline 2. Improved: 5-10 point decrease from baseline 3. Maintained: \<5 point decrease from baseline and \<5 point increase from baseline 4. Deteriorated: \>5 point increase from baseline |
| AOFAS Hindfoot and Ankle Score | 24 and 52 weeks | Subjects were asked to report pain, functionality and ability levels while the physician performed assessments based on alignment, abnormality, motion, and stability. The total score ranges from a low of zero to a high of 100, with subscales measuring pain (40 points), function (50 points), and alignment (10 points), with higher scores showing better outcomes. 1. Clinically significant improvement: ≥20 point increase from baseline 2. Improved: 10-20 point increase from baseline 3. Maintained: \<10 point increase from baseline and \<10 point decrease from baseline 4. Deteriorated: \>10 point decrease from baseline |
| SF-12 Physical Component Score | 24 and 52 weeks | The SF-12 Physical Component Score is a validated quality of life metric with a minimum of zero and a maximum of 100, with higher scores denoting higher quality of life. 1. Maintenance or improvement: ≥0 point increase from baseline 2. Slight Decline: 0-10 point decrease from baseline 3. Deteriorated: \>10 point decrease from baseline |
Countries
Canada, United States
Participant flow
Pre-assignment details
17 subjects excluded post-operatively
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Standard Rigid Fixation plus autograft
Standard of Care: Autologous Bone Graft | 142 |
| Group 2 Standard Rigid Fixation plus Augment® Bone Graft | 272 |
| Total | 414 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Total |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 13.4 | 55.9 years STANDARD_DEVIATION 14.5 | 56.47 years STANDARD_DEVIATION 14.14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 19 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) White | 131 Participants | 247 Participants | 378 Participants |
| Region of Enrollment Canada | 32 Participants | 67 Participants | 99 Participants |
| Region of Enrollment United States | 110 Participants | 205 Participants | 315 Participants |
| Sex: Female, Male Female | 61 Participants | 143 Participants | 204 Participants |
| Sex: Female, Male Male | 81 Participants | 129 Participants | 210 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 142 | 1 / 272 |
| other Total, other adverse events | 43 / 142 | 100 / 272 |
| serious Total, serious adverse events | 21 / 142 | 28 / 272 |
Outcome results
Primary
Subjects Fused at 24 Weeks (as Determined by CT Assessment)
An independent radiologist examined CT images for all patients' joints and determined whether or not the joint had at least 50% osseous bridging. If a patient demonstrated all joints having at least 50% osseous bridging, this patient was classified as fused.
Time frame: 24 weeks
Population: The mITT population consisted of 397 patients (414 patients in the Safety group minus 17 subjects excluded post-operatively).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Subjects Fused at 24 Weeks (as Determined by CT Assessment) | 85 Participants |
| Group 2 | Subjects Fused at 24 Weeks (as Determined by CT Assessment) | 159 Participants |
Secondary
AOFAS Hindfoot and Ankle Score
Subjects were asked to report pain, functionality and ability levels while the physician performed assessments based on alignment, abnormality, motion, and stability. The total score ranges from a low of zero to a high of 100, with subscales measuring pain (40 points), function (50 points), and alignment (10 points), with higher scores showing better outcomes. 1. Clinically significant improvement: ≥20 point increase from baseline 2. Improved: 10-20 point increase from baseline 3. Maintained: \<10 point increase from baseline and \<10 point decrease from baseline 4. Deteriorated: \>10 point decrease from baseline
Time frame: 24 and 52 weeks
Population: Analysis conducted on patients at 24 and 52 weeks time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | AOFAS Hindfoot and Ankle Score | Clinically Significant Improvement at 24 weeks | 94 Participants |
| Group 1 | AOFAS Hindfoot and Ankle Score | Improved at 24 weeks | 19 Participants |
| Group 1 | AOFAS Hindfoot and Ankle Score | Maintained at 24 weeks | 14 Participants |
| Group 1 | AOFAS Hindfoot and Ankle Score | Deteriorated at 24 weeks | 6 Participants |
| Group 1 | AOFAS Hindfoot and Ankle Score | Clinically Significant Improvement at 52 weeks | 106 Participants |
| Group 1 | AOFAS Hindfoot and Ankle Score | Improved at 52 weeks | 10 Participants |
| Group 1 | AOFAS Hindfoot and Ankle Score | Maintained at 52 weeks | 11 Participants |
| Group 1 | AOFAS Hindfoot and Ankle Score | Deteriorated at 52 weeks | 5 Participants |
| Group 2 | AOFAS Hindfoot and Ankle Score | Deteriorated at 52 weeks | 5 Participants |
| Group 2 | AOFAS Hindfoot and Ankle Score | Clinically Significant Improvement at 24 weeks | 180 Participants |
| Group 2 | AOFAS Hindfoot and Ankle Score | Clinically Significant Improvement at 52 weeks | 195 Participants |
| Group 2 | AOFAS Hindfoot and Ankle Score | Improved at 24 weeks | 27 Participants |
| Group 2 | AOFAS Hindfoot and Ankle Score | Maintained at 52 weeks | 19 Participants |
| Group 2 | AOFAS Hindfoot and Ankle Score | Maintained at 24 weeks | 35 Participants |
| Group 2 | AOFAS Hindfoot and Ankle Score | Improved at 52 weeks | 22 Participants |
| Group 2 | AOFAS Hindfoot and Ankle Score | Deteriorated at 24 weeks | 8 Participants |
Secondary
Foot Function Index (FFI)
The Foot Function Index (FFI) measures the impact of foot pathology on function in terms of pain, disability and activity restriction. The FFI is a self-administered index consisting of 23 items divided into 3 sub-scales. To obtain a sub-scale score, the item scores for a sub-scale are totaled and then divided by the maximum total possible for all of the sub-scale items which the subject indicated were applicable. Any item marked as not applicable is excluded from the total possible. Sub-scales are an average of the completed ratings within that sub-scale. The total foot function score is an average of the three sub-scale scores. Lower scores are indicative of better outcomes whereas higher scores indicate greater impairment. 1. Clinically significant improvement: ≥10 point decrease from baseline 2. Improved: 5-10 point decrease from baseline 3. Maintained: \<5 point decrease from baseline and \<5 point increase from baseline 4. Deteriorated: \>5 point increase from baseline
Time frame: 24 and 52 weeks
Population: Analysis conducted on patients at 24 and 52 weeks time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Foot Function Index (FFI) | Clinically Significant Improvement at 24 weeks | 106 Participants |
| Group 1 | Foot Function Index (FFI) | Improved at 24 weeks | 4 Participants |
| Group 1 | Foot Function Index (FFI) | Maintained at 24 weeks | 14 Participants |
| Group 1 | Foot Function Index (FFI) | Deteriorated at 24 weeks | 9 Participants |
| Group 1 | Foot Function Index (FFI) | Clinically Significant Improvement at 52 weeks | 114 Participants |
| Group 1 | Foot Function Index (FFI) | Improved at 52 weeks | 1 Participants |
| Group 1 | Foot Function Index (FFI) | Maintained at 52 weeks | 12 Participants |
| Group 1 | Foot Function Index (FFI) | Deteriorated at 52 weeks | 5 Participants |
| Group 2 | Foot Function Index (FFI) | Deteriorated at 52 weeks | 12 Participants |
| Group 2 | Foot Function Index (FFI) | Clinically Significant Improvement at 24 weeks | 190 Participants |
| Group 2 | Foot Function Index (FFI) | Clinically Significant Improvement at 52 weeks | 209 Participants |
| Group 2 | Foot Function Index (FFI) | Improved at 24 weeks | 19 Participants |
| Group 2 | Foot Function Index (FFI) | Maintained at 52 weeks | 12 Participants |
| Group 2 | Foot Function Index (FFI) | Maintained at 24 weeks | 16 Participants |
| Group 2 | Foot Function Index (FFI) | Improved at 52 weeks | 8 Participants |
| Group 2 | Foot Function Index (FFI) | Deteriorated at 24 weeks | 24 Participants |
Secondary
Pain at Fusion Site
Subjects were asked to report current pain level at the fusion site on a 100 mm Visual Analog Scale (with 0 being no pain and 100 being worst pain imaginable). 1. Clinically significant improvement: ≥20mm decrease from baseline 2. Detectable improvement: 10-20mm decrease from baseline 3. Maintained: \<10mm decrease from baseline and \<10mm increase from baseline 4. Deteriorated: \>10mm increase from baseline
Time frame: 24 and 52 weeks
Population: Analysis conducted on patients at 24 and 52 weeks time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Pain at Fusion Site | Deteriorated at 24 weeks | 10 Participants |
| Group 1 | Pain at Fusion Site | Clinically Significant Improvement at 24 weeks | 71 Participants |
| Group 1 | Pain at Fusion Site | Detectable Improvement at 24 weeks | 15 Participants |
| Group 1 | Pain at Fusion Site | Maintained at 24 weeks | 21 Participants |
| Group 1 | Pain at Fusion Site | Clinically Significant Improvement at 52 weeks | 81 Participants |
| Group 1 | Pain at Fusion Site | Detectable Improvement at 52 weeks | 11 Participants |
| Group 1 | Pain at Fusion Site | Maintained at 52 weeks | 19 Participants |
| Group 1 | Pain at Fusion Site | Deteriorated at 52 weeks | 9 Participants |
| Group 2 | Pain at Fusion Site | Deteriorated at 52 weeks | 8 Participants |
| Group 2 | Pain at Fusion Site | Deteriorated at 24 weeks | 20 Participants |
| Group 2 | Pain at Fusion Site | Clinically Significant Improvement at 52 weeks | 139 Participants |
| Group 2 | Pain at Fusion Site | Clinically Significant Improvement at 24 weeks | 144 Participants |
| Group 2 | Pain at Fusion Site | Maintained at 52 weeks | 44 Participants |
| Group 2 | Pain at Fusion Site | Detectable Improvement at 24 weeks | 20 Participants |
| Group 2 | Pain at Fusion Site | Detectable Improvement at 52 weeks | 27 Participants |
| Group 2 | Pain at Fusion Site | Maintained at 24 weeks | 39 Participants |
Secondary
Pain on Weight Bearing
Subjects were asked to stand and report pain on a 100 mm Visual Analog Scale (with 0 being no pain and 100 being worst pain imaginable). 1. Clinically significant improvement: ≥20mm decrease from baseline 2. Detectable improvement: 10-20mm decrease from baseline 3. Maintained: \<10mm decrease from baseline and \<10mm increase from baseline 4. Deteriorated: \>10mm increase from baseline
Time frame: 24 and 52 Weeks
Population: Analysis conducted on patients at 24 and 52 weeks time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Pain on Weight Bearing | Clinically Significant Improvement at 24 weeks | 87 Participants |
| Group 1 | Pain on Weight Bearing | Detectable Improvement at 24 weeks | 12 Participants |
| Group 1 | Pain on Weight Bearing | Maintained at 24 weeks | 12 Participants |
| Group 1 | Pain on Weight Bearing | Deteriorated at 24 weeks | 6 Participants |
| Group 1 | Pain on Weight Bearing | Clinically Significant Improvement at 52 weeks | 95 Participants |
| Group 1 | Pain on Weight Bearing | Detectable Improvement at 52 weeks | 8 Participants |
| Group 1 | Pain on Weight Bearing | Maintained at 52 weeks | 11 Participants |
| Group 1 | Pain on Weight Bearing | Deteriorated at 52 weeks | 4 Participants |
| Group 2 | Pain on Weight Bearing | Deteriorated at 52 weeks | 6 Participants |
| Group 2 | Pain on Weight Bearing | Clinically Significant Improvement at 24 weeks | 167 Participants |
| Group 2 | Pain on Weight Bearing | Clinically Significant Improvement at 52 weeks | 170 Participants |
| Group 2 | Pain on Weight Bearing | Detectable Improvement at 24 weeks | 14 Participants |
| Group 2 | Pain on Weight Bearing | Maintained at 52 weeks | 19 Participants |
| Group 2 | Pain on Weight Bearing | Maintained at 24 weeks | 25 Participants |
| Group 2 | Pain on Weight Bearing | Detectable Improvement at 52 weeks | 20 Participants |
| Group 2 | Pain on Weight Bearing | Deteriorated at 24 weeks | 13 Participants |
Secondary
SF-12 Physical Component Score
The SF-12 Physical Component Score is a validated quality of life metric with a minimum of zero and a maximum of 100, with higher scores denoting higher quality of life. 1. Maintenance or improvement: ≥0 point increase from baseline 2. Slight Decline: 0-10 point decrease from baseline 3. Deteriorated: \>10 point decrease from baseline
Time frame: 24 and 52 weeks
Population: Analysis conducted on patients at 24 and 52 weeks time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | SF-12 Physical Component Score | Slight Decline at 24 weeks | 22 Participants |
| Group 1 | SF-12 Physical Component Score | Maintenance or Improvement at 24 weeks | 106 Participants |
| Group 1 | SF-12 Physical Component Score | Deteriorated at 24 weeks | 5 Participants |
| Group 1 | SF-12 Physical Component Score | Maintenance or Improvement at 52 weeks | 117 Participants |
| Group 1 | SF-12 Physical Component Score | Slight Decline at 52 weeks | 14 Participants |
| Group 1 | SF-12 Physical Component Score | Deteriorated at 52 weeks | 1 Participants |
| Group 2 | SF-12 Physical Component Score | Slight Decline at 52 weeks | 33 Participants |
| Group 2 | SF-12 Physical Component Score | Slight Decline at 24 weeks | 38 Participants |
| Group 2 | SF-12 Physical Component Score | Maintenance or Improvement at 52 weeks | 206 Participants |
| Group 2 | SF-12 Physical Component Score | Maintenance or Improvement at 24 weeks | 203 Participants |
| Group 2 | SF-12 Physical Component Score | Deteriorated at 52 weeks | 2 Participants |
| Group 2 | SF-12 Physical Component Score | Deteriorated at 24 weeks | 8 Participants |