AMPLEX Ankle Fusion and Hindfoot

Not Applicable

Completed

Conditions: Arthrodesis Surgery Involving the Hindfoot or Ankle

Interventions: Device: AMPLEX
Procedure: Autogenous Bone Graft (ABG)

Registration Number: NCT03028415

Lead Sponsor: Ferring Pharmaceuticals

Brief Summary: To demonstrate that AMPLEX is non-inferior to autogenous bone graft (ABG) for bone fusion in a population indicated for single, double, or triple hindfoot arthrodesis or ankle arthrodesis surgery with supplemental graft material.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

Inclusion Criteria

Signed written informed consent
Indicated for ankle or hindfoot arthrodesis and require one of the following arthrodesis procedures:

Tibiotalar (ankle); Talocalcaneal (subtalar); Talonavicular; Calcaneocuboid; Double hindfoot (e.g., talonavicular and talocalcaneal joints); Triple hindfoot (subtalar, talonavicular and calcaneocuboid joints)

Presents with pain on weight-bearing of at least 40 mm on a 100 mm VAS at the area indicated for arthrodesis
Presents with at least one comorbid risk factors that warrant the use of supplemental autogenous bone or allograft:

Radiographic evidence of bone defect, deficit, subsidence or subchondral cyst; More than one joint to be fused; Involvement of other adjacent or nonadjacent joints; Large surface area; Intra-articular or extra-articular deformity; Post-traumatic arthritis; Diagnosis of osteoporosis

The Investigator determines if the joint space(s) can be adequately filled with graft material (AMPLEX or ABG) according to the following parameters:

Single hindfoot joint fusion: up to 5 cm^3; Double or triple hindfoot fusion: each individual joint up to 5 cm^3, but overall, not more than 10 cm3 for the full complement of joints; Ankle fusion: up to 10 cm^3

Each fused joint can be rigidly stabilized with with at least 1 and no more than 3 screws across the fusion plane. (Supplemental pins and staples may be used, as well as supplemental screws and plates external to the fusion site(s))
Willing and able to comply with all study requirements including all postoperative clinical and radiographic evaluations
For women of childbearing potential (not post-menopausal for 12 months or surgically sterile), a urine pregnancy test with a negative result must be obtained at screening and within 24 hours prior to procedure. These trial participants must commit to adequate birth control (e.g., oral contraceptive, two methods of barrier birth control, or abstinence) through the 78 week follow-up

Exclusion Criteria

Bone deficit requiring a structural graft
Charcot foot disease
Radiographic evidence of open physes
Prior arthroplasty, arthrodesis, major surgical repair or reconstruction of the index ankle or hindfoot joint(s)
Requires osteotomy or fusion of the midfoot joints
BMI greater than 45 kg/m^2
Documented medical history of, or radiographic evidence of, a bone disease (e.g. avascular necrosis) or other condition (e.g., osteolysis) that would preclude the subject from receiving screw fixation in the opinion of the surgeon
Requires intramedullary nail fixation or an external fixator
Comorbidity that would limit the ability to administer any functional measurements such as FAAM-ADL
Has at the time of surgery, a systemic infection or local infection at the site of surgery
Medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival or interfere with ambulation or rehabilitation (e.g., history of transient ischemic attack, stroke or liver disease)
HgbA1c level greater than or equal to 8%
Known hypersensitivity to any of the components of the product [e.g. B2A peptide, Hydroxyapatite (HA): beta-tricalcium phosphate (βTCP), ceramic granule]
Currently receiving treatment with a drug known to interfere with bone metabolism [e.g., systemic corticosteroid therapy (topical corticosteroid therapy is permissible), methotrexate]
Has previously received treatment with a drug known to interfere with bone metabolism [e.g., systemic corticosteroid therapy (topical corticosteroid therapy is permissible), methotrexate] and in the opinion of the investigator could continue to negatively interfere with bone metabolism or bone healing
History of any severe allergy or anaphylaxis, or a history of hypersensitivity to protein pharmaceuticals [e.g., monoclonal antibodies or gamma globulins, recombinant Bone Morphogenetic Proteins (BMPs)]
Medical condition requiring radiation, chemotherapy or immunosuppression
Have a prior or active history of malignancy (except for basal cell carcinoma of the skin)
Has a history of autoimmune disease known to affect bone metabolism. Examples include spondyloarthropathies (e.g., ankylosing spondylitis, Crohn's disease, and ulcerative colitis), Juvenile Arthritis, Grave's disease and Hashimoto's thyroiditis; Rheumatoid Arthritis is allowed
Have pathological or genetic liver disease or who have clinically significant, elevated baseline liver function enzymes
Has obvious and/or documented alcohol or illicit drug addictions
Is a prisoner in a correctional institution/facility
Actively involved in litigation or workman's compensation
Has participated in clinical studies evaluating investigational devices, pharmaceuticals or biologics within 6 months of randomization
Requires chronic therapeutic use of NSAID during the first 6 post-operative weeks (except aspirin up to 325 mg bid for cardiovascular protection and/or DVT prophylaxis)
Has previously been treated with, or exposed to, therapeutic levels of synthetic or recombinant BMPs
Requires chronic subcutaneous or intravenous heparin therapies

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AMPLEX	AMPLEX	-
Autogenous Bone Graft (ABG)	Autogenous Bone Graft (ABG)	-

Primary Outcome Measures

Name	Time	Method
Proportion of Subjects Who Met All Five Criteria for Subject Performance Composite (SPC) Endpoint	At week 52	Proportion of subjects who met all the following criteria for the SPC endpoint at 52 weeks: 1. Improvement in pain on weight-bearing at fusion site (≥20 mm reduction from baseline on 100 mm visual analog scale \[VAS\]); 2. Absence of significant graft harvest site pain (\<20 mm on 100 mm VAS); 3. Improvement in Foot and Ankle Ability Measure Activities of Daily Living subscale (FAAM-ADL) (≥8 points improvement from baseline); 4. Absence of device related or procedure related serious adverse events (up to week 52); 5. Absence of secondary surgical or nonsurgical interventions intended to promote fusion (up to week 52). The last observation carried forward was used for subjects with missing response status at 52 weeks.

Secondary Outcome Measures

Name	Time	Method
Proportion of Subjects Achieving Computerized Tomography (CT) Radiographic Fusion Success	At week 52	Defined as ≥50% bone bridging across the joint space for the full complement of joints in the absence of secondary surgical or nonsurgical interventions intended to promote fusion. The last observation carried forward was used for subjects with missing response status at 52 weeks.
Proportion of Subjects Achieving CT Radiographic Fusion Success	At week 24	Defined as ≥50% bone bridging across the joint space for the full complement of joints in the absence of secondary surgical or nonsurgical interventions intended to promote fusion.
Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS)	Baseline, and at week 52	Weight-bearing pain at the fusion site was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire. Subjects were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced, with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Improvement in pain on weight-bearing at the fusion site was defined as ≥ 20 mm reduction from baseline on 100 mm VAS, and is presented for this outcome measure.
Change From Baseline in FAAM-ADL	Baseline, and at week 52	Functional improvement was assessed using the Foot and Ankle Ability Measure Activities of Daily Living (FAAM-ADL) subscale, a subject self-assessment questionnaire that consists of 21 items pertaining to basic functional activities. Each item is scored on a 5 point Likert scale anchored by 4 (no difficulty at all) and 0 (unable to do). The total item subscale score ranges from 0 to 84, which are transformed to a scale of 0 to 100 as the final score. Higher scores represent a higher level of function, with 100 representing no dysfunction.
Change From Baseline in Short Form-12 (SF-12)	Baseline, and at week 52	The Short Form-12 (SF-12) Health Survey includes 12 questions from the SF-36 Health Survey. These include: 2 questions concerning physical functioning; 2 questions on role limitations because of physical health problems; 1 question on bodily pain; 1 question on general health perceptions; 1 question on vitality (energy/fatigue); 1 question on social functioning; 2 questions on role limitations because of emotional problems; and 2 questions on general mental health (psychological distress and psychological well-being). These eight domain scales were used to derive Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. All scores were calculated through scoring software. Domain scales and component summary scores ranged from 0 to 100, with a higher score considered better.
Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)	At week 52	Graft harvest site pain was assessed using a 100 mm visual analog scale (VAS), a subject self-assessment questionnaire, and was only assessed among subjects in the ABG group. Subjects in the ABG group were asked to mark the location on a 100 mm line corresponding to the amount of pain they experienced with 0 mm being "no pain" and 100 mm being "the worst pain imaginable". Absence of significant graft harvest site pain was defined as \<20 mm on 100 mm VAS, and is presented for this outcome measure.
Subject Performance Composite (SPC) Endpoint	At week 24	Proportion of subjects who met all the following criteria for the SPC endpoint at 24 weeks: 1. Improvement in pain on weight-bearing at fusion site (≥20 mm reduction from baseline on 100 mm visual analog scale \[VAS\]); 2. Absence of significant graft harvest site pain (\<20 mm on 100 mm VAS); 3. Improvement in Foot and Ankle Ability Measure Activities of Daily Living subscale (FAAM-ADL) (≥8 points improvement from baseline); 4. Absence of device related or procedure related serious adverse events (up to week 24); 5. Absence of secondary surgical or nonsurgical interventions intended to promote fusion (up to week 24).

Trial Locations

Locations (36): Michigan Orthopedic Center
🇺🇸
Lansing, Michigan, United States
St. Michael's Hospital
🇨🇦
Toronto, Ontario, Canada
Baylor St. Luke's Medical Center
🇺🇸
Houston, Texas, United States
Desert Orthopaedic Center
🇺🇸
Las Vegas, Nevada, United States
Physician Research Group
🇺🇸
Gilbert, Arizona, United States
California Pacific Orthopaedics
🇺🇸
San Francisco, California, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
Andrews Orthopaedic and Sports Medicine Center
🇺🇸
Gulf Breeze, Florida, United States
Emory Orthopaedic and Spine Hospital
🇺🇸
Atlanta, Georgia, United States
Midwest Orthopedics at Rush
🇺🇸
Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Sinai Hospital of Baltimore, Inc / Rubin Institute for Advanced Orthopedics
🇺🇸
Baltimore, Maryland, United States
Medstar
🇺🇸
Baltimore, Maryland, United States
Orthopaedic Associates of Michigan, Research and Education Institute
🇺🇸
Grand Rapids, Michigan, United States
TRIA Orthopaedic Center
🇺🇸
Bloomington, Minnesota, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Rutgers
🇺🇸
Newark, New Jersey, United States
University of Rochester School of Medicine
🇺🇸
Rochester, New York, United States
OrthoCarolina Research Institute, Inc.
🇺🇸
Charlotte, North Carolina, United States
Reconstructive Orthopaedic Associates
🇺🇸
Philadelphia, Pennsylvania, United States
Pennsylvania Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
University Orthopedics Center
🇺🇸
State College, Pennsylvania, United States
Campbell Clinic Orthopaedics
🇺🇸
Germantown, Tennessee, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States
Texas Tech University Health Sciences Center
🇺🇸
Lubbock, Texas, United States
University of Virginia Health System
🇺🇸
Charlottesville, Virginia, United States
Central Alberta Orthopedics
🇨🇦
Red Deer, Alberta, Canada
St. Paul's Hospital
🇨🇦
Vancouver, British Columbia, Canada
Ottawa Hospital Research Institute
🇨🇦
Ottawa, Ontario, Canada
Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
University of Laval
🇨🇦
Quebec City, Quebec, Canada
University of Colorado School of Medicine
🇺🇸
Aurora, Colorado, United States
Arizona Research Center
🇺🇸
Phoenix, Arizona, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
University of Alberta System
🇨🇦
Edmonton, Alberta, Canada
Queen Elizabeth II Health Sciences Centre
🇨🇦
Halifax, Nova Scotia, Canada