Clinical trial NCT01305356: Augment® Injectable Bone Graft Compared to Autologous Bone Graft as a Bone Regeneration Device in Hindfoot Fusions
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Degenerative Joint Disease
Congenital Deformity
Arthritis
Osteoarthritis
Rheumatoid Arthritis
Keywords: 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)
Lead sponsor: BioMimetic Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-02-28
Enrollment: 299
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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

Eligibility criteria: 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

Primary outcomes:
measure: Pain on Weight Bearing
timeFrame: Baseline, 9, 12, 16, 24, 36, and 52 weeks
Secondary outcomes:
measure: Foot Function Index (FFI)
timeFrame: Baseline, 9, 12, 16, 24, 36, and 52 weeks
measure: AOFAS Hindfoot and Ankle Score
timeFrame: Baseline, 9, 12, 16, 24, 36, and 52 weeks
measure: Fusion Site Pain
timeFrame: Baseline, 9, 12, 16, 24, 36, and 52 weeks
measure: SF-12 Physical Component Score
timeFrame: Baseline, 9, 12, 16, 24, 36, and 52 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Orthopaedic Research Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Glenview
country: United States
facility: Illinois Bone & Joint Institute, Ltd.
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Union Memorial Hospital
state: Maryland
city: East Lansing
country: United States
facility: Mid Michigan Orthopaedic Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Orthopaedic Associates of Michigan, PC
state: Michigan
city: Las Vegas
country: United States
facility: Desert Orthopaedic Center
state: Nevada
city: Newark
country: United States
facility: University of Medicine & Dentistry of New Jersey
state: New Jersey
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: OrthoCarolina, PA
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Orthopaedic
state: Ohio
city: Columbus
country: United States
facility: Orthopedic Foot & Ankle Center
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research Institute, Inc.
state: Oklahoma
city: Philadelphia
country: United States
facility: The Rothman Institute
state: Pennsylvania
city: Memphis
country: United States
facility: Campbell Clinic / InMotion Orthopaedic Research Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Health Research & Education Institute
state: Texas
city: Houston
country: United States
facility: St. Luke's Episcopal Hospital
state: Texas
city: Calgary
country: Canada
facility: Life Mark Health Centre
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Services
state: Nova Scotia
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Stryker Trauma and Extremities
name: Stephen Roach
role: STUDY_DIRECTOR
affiliation: University Orthopaedics, Inc.
name: Christopher DiGiovanni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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 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.