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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01305356
• Other study ID #: BMTI-2010-01
• Status: Completed
• Phase: N/A
• Start date: March 2011
• Est. completion date: April 2014

Study information

• Verified date: December 2018
• Source: BioMimetic Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Other known NCT identifiers

• NCT01008891

Recruitment information / eligibility

• Status: Completed
• Enrollment: 299
• Est. completion date: April 2014
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Congenital Abnormalities
• Congenital Deformity
• Degenerative Joint Disease
• Joint Diseases
• Osteoarthritis
• Rheumatoid Arthritis

Intervention

Device:
• Augment® Injectable Bone Graft
Implantation of up to 9cc of Augment® Injectable Bone Graft

Procedure:
• Autologous bone graft
Implantation of up to 9cc of autologous bone graft

Locations

Country	Name	City	State
Canada	Life Mark Health Centre	Calgary	Alberta
Canada	Queen Elizabeth II Health Services	Halifax	Nova Scotia
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
United States	Union Memorial Hospital	Baltimore	Maryland
United States	OrthoCarolina, PA	Charlotte	North Carolina
United States	Cleveland Clinic Orthopaedic	Cleveland	Ohio
United States	Orthopedic Foot & Ankle Center	Columbus	Ohio
United States	Texas Health Research & Education Institute	Dallas	Texas
United States	Mid Michigan Orthopaedic Institute	East Lansing	Michigan
United States	Illinois Bone & Joint Institute, Ltd.	Glenview	Illinois
United States	Orthopaedic Associates of Michigan, PC	Grand Rapids	Michigan
United States	St. Luke's Episcopal Hospital	Houston	Texas
United States	Desert Orthopaedic Center	Las Vegas	Nevada
United States	Loyola University Medical Center	Maywood	Illinois
United States	Campbell Clinic / InMotion Orthopaedic Research Center	Memphis	Tennessee
United States	Hospital for Special Surgery	New York	New York
United States	University of Medicine & Dentistry of New Jersey	Newark	New Jersey
United States	Health Research Institute, Inc.	Oklahoma City	Oklahoma
United States	The Rothman Institute	Philadelphia	Pennsylvania
United States	University of Rochester Medical Center	Rochester	New York
United States	California Pacific Medical Center	San Francisco	California
United States	Tucson Orthopaedic Research Center	Tucson	Arizona
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
BioMimetic Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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 ß-TCP-Col — View Citation

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 phospha — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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. Lower scores are indicative of better outcomes whereas higher scores indicate greater impairment.	Baseline, 9, 12, 16, 24, 36, and 52 weeks
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.	Baseline, 9, 12, 16, 24, 36, and 52 weeks
Secondary	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
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.	Baseline, 9, 12, 16, 24, 36, and 52 weeks