Augment® Injectable Bone Graft Compared to Autologous Bone Graft as a Bone Regeneration Device in Hindfoot Fusions

Study Overview
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Brief Summary
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STUDY OBJECTIVES: To demonstrate equivalent clinical and radiologic outcomes as gold standard (Autologous Bone Graft) in a representative clinical model (hindfoot fusions) STUDY HYPOTHESIS: Augment® Injectable is an equivalent bone grafting substitute to autologous bone graft in applications as shown by superiority analysis for safety and non-inferiority analysis for effectiveness STUDY RATIONALE: To evaluate a fully synthetic bone graft material 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 Autologous Bone Graft without necessitating an additional invasive procedure to harvest the graft

Detailed Description
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STUDY DESIGN: Prospective, randomized, controlled, non-inferiority, multi-center trial NUMBER OF STUDY CENTERS: 25 NUMBER OF SUBJECTS: 299 Subjects (see Study Population). The subject population included subjects enrolled in 3 separate Clinical Trials. (BMTI-2006-01, BMTI-2009-01, and BMTI-2010-01) STUDY POPULATION: Male and female subjects 18 years of age or older requiring a hindfoot fusion procedure involving a bone grafting procedure. TREATMENT GROUPS: Group I: Standard Rigid Fixation + Autologous Bone Graft Group II: Standard Rigid Fixation + Augment® Injectable Bone Graft Subjects will be randomized in a 2:1 ratio (Augment® Injectable:Autologous Bone Graft). ROUTE OF ADMINISTRATION: Investigational device is manually implanted inside and around the fusion space to ensure Augment® Injectable Bone Graft (beta-TCP/bovine collagen matrix +rhPDGF-BB) or autologous bone graft is contained within the joint space STUDY DURATION: Twenty-four month follow-up post-surgery

Official Title
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A Prospective, Randomized, Controlled, Multi-Center, Pivotal Human Clinical Trial to Evaluate the Safety and Effectiveness of Augment® Injectable Bone Graft Compared to Autologous Bone Graft as a Bone Regeneration Device in Hindfoot Fusions

Conditions
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Osteoarthritis, Degenerative Joint Disease, Congenital Deformity, Arthritis, Rheumatoid Arthritis

Intervention / Treatment
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* Device: Augment® Injectable Bone Graft
* Procedure: Autologous bone graft


Participation Criteria
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Eligibility Criteria
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KEY INCLUSION CRITERIA: at least 18 years old and considered skeletally mature diagnosed with degenerative joint disease (DJD) affecting the hindfoot due to a congenital or acquired deformity, osteoarthritis, rheumatoid arthritis, post- traumatic arthritis or ankylosing spondylitis of the ankle, subtalar, calcaneocuboid, and/or talonavicular joints requires one of the following hindfoot fusion proceduress with supplemental bone graft/substitute: ankle fusion (tibiotalar), subtalar fusion (talocalcaneal), calcaneocuboid fusion, talonavicular fusion, triple arthrodesis (subtalar, talonavicular and calcaneocuboid joints) OR double fusions (any combination of any two of the following: subtalar, talonavicular and calcaneocuboid joints) fusion site able to be rigidly stabilized with no more than 3 screws across the fusion site supplemental pins or staples allowed supplemental screws external to the fusion site(s) allowed signed informed consent document, independent, ambulatory, and can comply with all post-operative evaluations and visits KEY EXCLUSION CRITERIA: undergone previous fusion surgery at the proposed location, i.e., revision of a failed fusion more than one previous procedure at the involved joints retained hardware spanning the joint(s) intended for fusion procedure anticipated to require plate fixation (including claw plates), IM nails or more than 3 screws to achieve rigid fixation based on pre-op planning procedure expected to require more than 9cc of graft material based on pre-op planning procedure expected to require structural bone graft, allograft, bone graft substitute, platelet rich plasma (PRP) or bone marrow aspirate procedure expected to require a pantalar fusion, i.e., fusion of ankle plus all hindfoot joints (talonavicular, subtalar, and calcaneocuboid) or an ankle fusion in combination with any hindfoot fusion radiographic evidence of bone cysts, segmental defects or growth plate fracture near the fusion site that could negatively impact the proposed fusion procedure tested positive or been treated for a malignancy in the past or is suspected of having a malignancy or currently undergoing radio- or chemotherapy treatment for a malignancy anywhere in the body, whether adjacent to or distant from the proposed surgical site pre-existing sensory impairment, e.g., diabetics with baseline sensory impairment, which limits ability to perform objective functional measurements and may be at risk for complications - diabetics not sensitive to the 5.07 monofilament (Semmes-Weinstein) are to be excluded metabolic disorder known to adversely affect the skeleton other than primary osteoporosis or diabetes, e.g., renal osteodystrophy or hypercalcemia use of chronic medications known to affect the skeleton, e.g., glucocorticoid usage > 10mg/day pre-fracture neuromuscular or musculoskeletal deficiency which limits the ability to perform objective functional measurements physically or mentally compromised, e.g., current treatment for a psychiatric disorder, senile dementia, Alzheimer's disease, etc., to the extent that the Investigator judges the subject to be unable or unlikely to remain compliant allergic to yeast-derived products or bovine collagen or other bovine-sourced products received an investigational therapy within 30 days of proposed surgery or during the follow-up phase of the study is a prisoner, known or suspected transient or a history of drug/alcohol abuse within the 12 months prior to screening pregnant or intending to become pregnant within 12 months of the study procedure morbidly obese defined as BMI > 45 kg/m2 currently has an acute infection at the surgical site

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Augment® Injectable Bone Graft<br>Standard rigid fixation + Augment® Injectable Bone Graft (beta-TCP/bovine collagen matrix + rhPDGF-BB) | Device: Augment® Injectable Bone Graft<br>* Implantation of up to 9cc of Augment® Injectable Bone Graft<br>|
| Active Comparator: Autologous bone graft<br>Standard Rigid Fixation + Autologous bone graft | Procedure: Autologous bone graft<br>* Implantation of up to 9cc of autologous bone graft<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, 9, 12, 16, 24, 36, and 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 all ranging from 0-100. 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 and ranges from 0-100. Lower scores are indicative of better outcomes whereas higher scores indicate greater impairment. | Baseline, 9, 12, 16, 24, 36, and 52 weeks | 
| 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. | Baseline, 9, 12, 16, 24, 36, and 52 weeks | 
| Fusion Site Pain | 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). | Baseline, 9, 12, 16, 24, 36, and 52 weeks | 
| 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. | Baseline, 9, 12, 16, 24, 36, and 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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degenerative joint disease, DJD, joint fusion, hindfoot, congenital deformity, osteoarthritis, rheumatoid arthritis, post-traumatic arthritis, ankylosing spondylitis, Augment(tm) Injectable Bone Graft, autologous bone graft, autogenous bone graft, beta-TCP, bovine collagen, rhPDGF(bb)