Safety and Efficacy Study of Autologous Concentrated Bone Marrow Aspirate (cBMA) for Critical Limb Ischemia (CLI)

Not Applicable

Terminated

Conditions: Peripheral Arterial Disease
Peripheral Vascular Disease
Critical Limb Ischemia

Interventions: Device: Bone marrow concentration device
Procedure: Placebo procedure (sham)

Registration Number: NCT01049919

Lead Sponsor: Zimmer Biomet

Brief Summary: This trial will evaluate the safety and efficacy of concentrated bone marrow aspirate (cBMA) to prevent or delay major amputation and/or death in subjects with critical limb ischemia (CLI) due to severe peripheral arterial disease (PAD).

Detailed Description: This is a prospective, randomized, double-blind, placebo controlled, multicenter trial intended for subjects with critical limb ischemia (CLI) that are unsuitable for revascularization. The investigational treatment utilizes autologous concentrated bone marrow aspirate (cBMA) at the point of care. The bone marrow aspirate is obtained from the subject's hip, concentrated with a bone marrow concentration device, and delivered intramuscularly to the affected limb. Subjects meeting the inclusion/exclusion criteria will be randomized to receive either the investigational treatment (cBMA) or a placebo control (sham treatment).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 153

Inclusion Criteria

Unilateral or bilateral lower extremity ischemia due to advanced peripheral arterial disease
Unsuitable for revascularization
Minor tissue loss (Rutherford Category 5) or ischemic rest pain (Rutherford Category 4) with ABI ≤ 0.6, or TBI ≤ 0.4, or TcPO2 ≤ 50 mm Hg
Competent to give consent
No current malignancy or history of previous malignancy within the last five years, with the exception of adequately treated non-melanoma skin cancer (evidence of standard preventative cancer screenings required)

Exclusion Criteria

Major tissue loss (Rutherford Category 6)
Diabetics on oral or insulin therapy with uncontrolled or untreated proliferative retinopathy (evidence of retinal exam required)
Poorly controlled diabetes mellitus with HbA1C > 10% (evidence of HbA1C test required)
Uncompensated congestive heart failure (New York Heart Association Class IV) and/or other conditions that preclude general anesthesia
Myocardial infarction or stroke within last 90 days
Elevated liver function tests (AST or ALT more than twice normal upper limit)
Renal disease (creatinine > 2.5 mg/dl) or chronic hemodialysis
White blood cell count < 3,000/µL or > 15,000/µL, platelet count < 100,000/µL, or hematocrit < 32%
Topical growth hormone therapy within last 90 days, or injected growth hormone therapy within last 180 days
Disease of central nervous system and/or other conditions that impair cognitive function
Two or more episodes of pulmonary embolus with a documented DVT in index leg or history of DVT in index leg without evidence of clot resolution
Current infection of index leg
Pregnant women (negative urine pregnancy test required)
Lower extremity venous disease with pitting edema in index leg
Recent history (in the 6 months prior to screening) of bone marrow disease or treatment with any medication or procedure which adversely affects the bone marrow and would prohibit transplantation
Current osteomyelitis in index leg
Existing HIV diagnosis
Organ transplant recipients
Known terminal disease process with life expectancy less than one year
Severe concomitant disease(s) or any additional condition(s) which the investigator feels constitute(s) criteria for exclusion of a particular subject
Major amputation required within 30 days
Inclusion in any other clinical study that may affect the outcome of this study
Uncorrected stenosis(es) of greater than 50% in the common and/or external iliac artery and/or common femoral artery of the index leg.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Concentrated bone marrow aspirate (cBMA)	Bone marrow concentration device	Collection of autologous bone marrow aspirate and point-of-care concentration using the bone marrow concentration device, followed by intramuscular injection of concentrated bone marrow aspirate (cBMA) into the affected limb
Placebo control (sham)	Placebo procedure (sham)	Placebo procedure (sham) consists of simulated bone marrow aspiration followed by simulated intramuscular injections into the affected limb

Primary Outcome Measures

Name	Time	Method
Occurrence of Major Amputation or Death	52 weeks	Occurrence of major amputation (above the ankle joint) or death.

Secondary Outcome Measures

Name	Time	Method
Visual Analog Scale (VAS) - Pain	52 weeks	Pain reported at the 52-week follow-up visit as assessed on the visual analog scale (VAS). Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain." The distance from the beginning of the line is measured and reported in centimeters (cm), with 0 representing no pain and 10 representing the worst possible pain.
Six-Minute Walk Test	52 weeks	Measurement (in meters) of the total distance a participant is able to walk in 6 minutes. Since ability to walk is related to the condition of the affected limb, this measure is tied to limb pain and function. If a participant had multiple limbs included in the study, each limb was evaluated separately. Only one limb could be included in the study at a time.

Trial Locations

Locations (25): Piedmont Hospital
🇺🇸
Atlanta, Georgia, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University Hospitals Cleveland Medical Center
🇺🇸
Cleveland, Ohio, United States
The Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Remington-Davis
🇺🇸
Columbus, Ohio, United States
Temple University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
VA Pittsburgh Healthcare System
🇺🇸
Pittsburgh, Pennsylvania, United States
Indiana University School of Medicine
🇺🇸
Indianapolis, Indiana, United States
Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
The Methodist Hospital
🇺🇸
Houston, Texas, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States
Nebraska-Western Iowa VA Healthcare System
🇺🇸
Omaha, Nebraska, United States
Aurora St. Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
University of California-Davis Medical Center
🇺🇸
Sacramento, California, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
UMass Memorial Health Care
🇺🇸
Worcester, Massachusetts, United States
Saint Luke's Hospital
🇺🇸
Kansas City, Missouri, United States
Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
Holy Name Medical Center
🇺🇸
Teaneck, New Jersey, United States
The Mount Sinai Hospital
🇺🇸
New York, New York, United States
Weill Cornell Medical College / New York-Presbyterian Hospital
🇺🇸
New York, New York, United States
Providence Sacred Heart Medical Center
🇺🇸
Spokane, Washington, United States
University of Virginia Hospital
🇺🇸
Charlottesville, Virginia, United States
Central Arkansas Veterans Healthcare System
🇺🇸
Little Rock, Arkansas, United States
University of Miami
🇺🇸
Miami, Florida, United States