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

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

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

Study Overview

• Status: Completed
• Conditions: Arthritis; Osteoarthritis; Rheumatoid Arthritis; Degenerative Joint Disease; Congenital Deformity
• Intervention / Treatment: Device: Augment® Injectable Bone Graft; Procedure: Autologous bone graft

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 299
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Life Mark Health Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • St. Paul's Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H3A7
      • Queen Elizabeth II Health Services
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5C1R6
      • St. Michael's Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
    • Tucson, Arizona, United States, 85712
      • Tucson Orthopaedic Research Center
  • California
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center
  • Illinois
    • Glenview, Illinois, United States, 60025
      • Illinois Bone & Joint Institute, Ltd.
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Union Memorial Hospital
  • Michigan
    • East Lansing, Michigan, United States, 48823
      • Mid Michigan Orthopaedic Institute
    • Grand Rapids, Michigan, United States, 49525
      • Orthopaedic Associates of Michigan, PC
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Desert Orthopaedic Center
  • New Jersey
    • Newark, New Jersey, United States, 07101
      • University Of Medicine & Dentistry Of New Jersey
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • OrthoCarolina, PA
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Orthopaedic
    • Columbus, Ohio, United States, 43231
      • Orthopedic Foot & Ankle Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Health Research Institute, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • The Rothman Institute
  • Tennessee
    • Memphis, Tennessee, United States, 38138
      • Campbell Clinic / InMotion Orthopaedic Research Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Health Research & Education Institute
    • Houston, Texas, United States, 77030
      • St. Luke's Episcopal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Augment® Injectable Bone Graft; Standard rigid fixation + Augment® Injectable Bone Graft (beta-TCP/bovine collagen matrix + rhPDGF-BB)	Device: Augment® Injectable Bone Graft; Implantation of up to 9cc of Augment® Injectable Bone Graft
ACTIVE_COMPARATOR: Autologous bone graft; Standard Rigid Fixation + Autologous bone graft	Procedure: Autologous bone graft; Implantation of up to 9cc of autologous bone graft

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BioMimetic Therapeutics
• Investigators: Study Director: Stephen Roach, Stryker Trauma GmbH; Principal Investigator: Christopher DiGiovanni, MD, University Orthopaedics, Inc.

Publications and helpful links

General Publications

• Daniels TR, Younger AS, Penner MJ, Wing KJ, Le IL, Russell IS, Lalonde KA, Evangelista PT, Quiton JD, Glazebrook M, DiGiovanni CW. Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated With rhPDGF-BB in Combination With a beta-TCP-Collagen Matrix. Foot Ankle Int. 2015 Jul;36(7):739-48. doi: 10.1177/1071100715576370. Epub 2015 Apr 6.
• DiGiovanni CW, Lin SS, Baumhauer JF, Daniels T, Younger A, Glazebrook M, Anderson J, Anderson R, Evangelista P, Lynch SE; North American Orthopedic Foot and Ankle Study Group. Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/beta-TCP): an alternative to autogenous bone graft. J Bone Joint Surg Am. 2013 Jul 3;95(13):1184-92. doi: 10.2106/JBJS.K.01422.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2011
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: February 25, 2011
• First Submitted That Met QC Criteria: February 25, 2011
• First Posted (ESTIMATE): February 28, 2011

Study Record Updates

• Last Update Posted (ACTUAL): December 26, 2018
• Last Update Submitted That Met QC Criteria: December 4, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: osteoarthritis; rheumatoid arthritis; ankylosing spondylitis; autologous bone graft; DJD; degenerative joint disease; post-traumatic arthritis; joint fusion; hindfoot; congenital deformity; Augment(tm) Injectable Bone Graft; autogenous bone graft; beta-TCP; bovine collagen; rhPDGF(bb)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Osteoarthritis; Congenital Abnormalities; Joint Diseases
• Other Study ID Numbers: BMTI-2010-01