An Efficacy and Safety Study of Ixmyelocel-T in Patients With Critical Limb Ischemia (CLI) (REVIVE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Aastrom Biosciences
ClinicalTrials.gov Identifier:
NCT01483898
First received: November 30, 2011
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

This study is designed to evaluate the efficacy and safety of ixmyelocel-T, a patient-specific expanded multicellular therapy, for the treatment of patients with critical limb ischemia (CLI). The study is a randomized, vehicle controlled (placebo)study in CLI patients who have no option for revascularization procedures. All patients randomized will undergo a small volume bone marrow aspiration in a 15-minute outpatient or in-office procedure. All patients will receive injections of either ixmyelocel-T or vehicle-control into their pre-identified index leg. Patients will be followed for 18 months.


Condition Intervention Phase
Critical Limb Ischemia
Biological: Ixmyelocel-T
Other: Vehicle Control
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study To Evaluate The Efficacy, Safety, And Tolerability Of Ixmyelocel-T In Subjects With Critical Limb Ischemia And No Options For Revascularization

Resource links provided by NLM:


Further study details as provided by Aastrom Biosciences:

Primary Outcome Measures:
  • Amputation free survival (AFS) at 12 months post-injection [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The primary objective will be to assess the efficacy of ixmyelocel-T compared to placebo (vehicle control) on AFS at 12 months post-injection in CLI patients with no options for revascularization. Amputation free survival is defined as time to the first occurrence of either major amputation (above the talus) in the index leg or all-cause mortality (death).


Secondary Outcome Measures:
  • Percent of patients with adverse events [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    A secondary objective will be to evaluate the overall safety and tolerability of ixmyelocel-T versus placebo in patients with CLI from time of aspiration through 18 months post-treatment/follow-up by % of patients with adverse events.

  • Percent of patients with complete wound closure by Month 12 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    A secondary objective is to assess the percent of patients with at least 1 ischemic wound on the index leg that is present at Visit 3 (preinjection) having complete closure by Month 12.

  • Percent of patients experiencing a major cardiac event (MACE) by Months 6, 12, and 18 [ Time Frame: 6, 12 and 18 months ] [ Designated as safety issue: No ]
    % of patients experiencing a MACE event defined as cardiovascular mortality, myocardial infarction, chest pain requiring hospitalization, or stroke.


Enrollment: 41
Study Start Date: February 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ixmyelocel-T Biological: Ixmyelocel-T
On Day 14, 20 intramuscular injections of either ixmyelocel-T or vehicle control on pre-identified index leg.
Placebo Comparator: Vehicle Control Other: Vehicle Control
On Day 14, 20 intramuscular injections of either ixmyelocel-T or vehicle control on pre-identified index leg.

  Eligibility

Ages Eligible for Study:   35 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and nonpregnant, nonlactating females
  • Ages 35 to 90 years of age
  • Diagnosis of CLI with tissue loss (corresponding to Rutherford Category 5; see Appendix B) having an ulcer size of at least 0.5 cm2, a smaller sized ulcer penetrating into the subcutaneous tissue, and/or gangrene (dry). In addition, the subject must have ONE of the following documented at screening:

    • Ankle systolic pressure < 70 mm Hg
    • Toe systolic pressure < 50 mm Hg
    • TcPO2 < 30 mm Hg (in a supine position)
  • Subjects must have no reasonable standard-of-care options for surgical or endovascular revascularization interventions
  • Subjects must have the following:

    • A narrative documenting the reasons why the site vascular specialist considers the subject "no option". A vascular specialist will be the principal investigator (PI) or subinvestigator and is defined as: vascular surgeon, interventional cardiologist, certified vascular medicine specialist, or interventional radiologist; AND
    • Secondary confirmation by an independent Eligibility Review Committee (ERC; see Section 8.1) after review of appropriate documents including, but not limited to: imaging results, medical records, surgical history, site vascular specialist narrative documenting reasons for "no option," and/or lab reports.
  • Major amputation in the index leg or death is not anticipated within 3 months of screening in the opinion of the vascular specialist (who must be the PI or subinvestigator)
  • In the opinion of the investigator, the subject is controlled on medical therapy indicated for CLI (unless there is a documented contraindication or intolerance)
  • Subject is current with all age-appropriate American Cancer Society (ACS) or similar (e.g., United States Preventative Service Task Force) screening guidelines
  • Given medical history and concurrent medication, the subject is an acceptable candidate for bone marrow aspiration and intramuscular injection procedures in the opinion of the Investigator
  • Subject is willing and able to comply with the scheduled visits, aspiration/injection procedure, wound care instructions treatment plan, and other study procedures for the duration of the study
  • Provide a personally-signed and dated informed consent document indicating that the subject (or a legally-acceptable representative, if permitted by the site's Investigational Review Board [IRB]) has been informed of all pertinent aspects of the study

Exclusion Criteria:

Patients presenting with any of the following will not be randomized:

Disease-specific:

  • Failed open surgical revascularization (on index leg) within 4 weeks of screening Visit 1
  • Acute limb-threatening ischemia, trauma, known non-atherosclerotic vascular disease (e.g., temporal/giant cell arteritis, Takayasu's arteritis, Raynaud's occlusive disease, Buerger's disease), embolic disease, aortoiliac disease with > 50% stenosis, or history of hypercoagulable states
  • Advanced CLI (i.e., nonsalvageable) defined as Rutherford Category 6
  • Clinical evidence of invasive infection in index leg (e.g., cellulitis, osteomyelitis, wet gangrene)
  • At screening, non-heel wound size of > 20 cm2 (excluding toe gangrene); or wounds on the heel > 10 cm2 on the index leg as measured by the Wound Core Lab (WCL) from photographs (and/or acetates) provided by the site
  • Previous amputation at or above the talus in the index leg Medical History
  • Hemoglobin A1c (HbA1c) ≥ 10% at screening
  • Diabetic subjects with uncontrolled or untreated proliferative retinopathy as determined by dilated eye exam (by qualified eye care professional as per American Diabetes Association guidelines)
  • Blood clotting disorder not caused by medication (e.g., thrombophilia)
  • Active non-basal cell cutaneous malignancy requiring surgery, chemotherapy, and/or radiation in the past 12 months
  • Current documented drug or alcohol abuse that would interfere with the subject's compliance with study procedures
  • Known allergies to any equine, porcine, or bovine products
  • Body mass index (BMI) ≥ 50 kg/m2 at screening
  • Established chronic kidney disease (CKD) requiring dialysis (Stage 5); estimated creatinine clearance < 15 mg/mL/min at screening
  • Systolic blood pressure (SBP) > 200 mm Hg or diastolic blood pressure (DBP) > 120 mm Hg or papilledema noted via ophthalmoscope at screening physical exam
  • Within 3 months prior to screening, a clinically significant history of cardiac disease

Laboratory Parameters:

  • Abnormal laboratory values (performed at central lab) at screening:

    • Platelets < 50,000 μL
    • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 3 times the upper limit of normal (ULN)
    • Human immunodeficiency virus 1 (HIV 1), HIV 2, or syphilis positive (rapid plasma reagin [RPR])
    • Active hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV); Exclusionary Procedures, Devices, or Medication
  • Exposure to immunosuppressive therapy for oncologic or chronic non-oncologic reasons in the prior 12 months or expected requirement over the course of the study (e.g., chemotherapy, radiation therapy, methotrexate)
  • Concurrent participation in another clinical trial or receiving experimental medication within 30 days of screening or having previously been exposed to Aastrom's ixmyelocel T product [previously known as tissue repair cells (TRC), cardiac repair cells (CRC), vascular repair cells (VRC)]
  • On the index leg, use of concomitant wound treatments not currently approved for ischemic wound-healing within 30 days prior to screening or plans to initiate new, nonstandard-of-care treatments to the index leg during the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01483898

  Hide Study Locations
Locations
United States, Alabama
Cardio-Thoracic Surgeons, P.C.
Birmingham, Alabama, United States, 35243
University Of Alabama At Birmingham
Birmingham, Alabama, United States, 35294
Cardiology PC
Birmingham, Alabama, United States, 35211
United States, Arizona
Arizona Heart Institute
Phoenix, Arizona, United States, 85006
Carl T. Hayden VA Medical Center
Phoenix, Arizona, United States, 85012
University of Arizona
Tucson, Arizona, United States, 85724
United States, Arkansas
Arkansas Primary Care Clinic, P.A.
Little Rock, Arkansas, United States, 72204
Central Arkansas Veteran's Healthcare System
Little Rock, Arkansas, United States, 72205
United States, California
John Muir Medical Center - Concord Campus
Concord, California, United States, 94520
VA Loma Linda Healthcare
Loma Linda, California, United States, 92357
UCLA Gonda Venous Center & Ambulatory Procedure Unit
Los Angeles, California, United States, 90095
Sutter Medical Group - Cardiology
Sacramento, California, United States, 95819
Kaiser Permanente Medical Center
San Diego, California, United States, 92120
University of California San Diego Medical Center
San Diego, California, United States, 92103
University of California San Francisco - Division of Vascular and Endovascular Surgery
San Francisco, California, United States, 94143-0222
United States, Colorado
University of Colorado Denver - Anschutz Medical Campus
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale School of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
Bethesda Memorial Hospital - Clinical Research Center
Boynton Beach, Florida, United States, 33435
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
Malcom Randall Veterans Affairs Medical Center
Gainesville, Florida, United States, 32608
Florida Research Network, LLC
Gainesville, Florida, United States, 32605
First Coast Cardiovascular Institute, P.A.
Jacksonville, Florida, United States, 32216
University of Miami Hospital
Miami, Florida, United States, 33136
Orlando Health
Orlando, Florida, United States, 32806
Cardiology Consultants
Pensacola, Florida, United States, 32501
Baptist Hospital
Pensacola, Florida, United States, 32501
Grove Place Surgery Center
Vero Beach, Florida, United States, 32960
United States, Georgia
Vascular Surgical Associates, P.C.
Marietta, Georgia, United States, 30060
United States, Illinois
University of Illinois at Chicago - Clinical Sciences North
Chicago, Illinois, United States, 60612
Rush University Medical Center
Chicago, Illinois, United States, 60612
Memorial Medical Center
Springfield, Illinois, United States, 62702
United States, Indiana
Indiana/Ohio Heart
Fort Wayne, Indiana, United States, 46804
St. Vincent Medical Group, Inc.
Indianapolis, Indiana, United States, 46290
United States, Iowa
Heartland Vascular Medicine and Surgery
Windsor Heights, Iowa, United States, 50324
United States, Louisiana
Ochsner Clinic foundation
New Orleans, Louisiana, United States, 70121
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Union Memorial Hospital
Baltimore, Maryland, United States, 21218
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Boston Medical Center
Boston, Massachusetts, United States, 02118
UMASS Memorial Health Care
Worcester, Massachusetts, United States, 01655
United States, Michigan
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, United States, 48105
Cardiology and Vascular Associates, P.C.
Berkley, Michigan, United States, 48072
Oakwood Hospital and Medical Center
Dearborn, Michigan, United States, 48124
John D. Dingell VA Medical Center
Detroit, Michigan, United States, 48201
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Michigan Vascular Research Center
Flint, Michigan, United States, 48507
Integrated Vascular Vein Center of Michigan
Grand Blanc, Michigan, United States, 48439
Michigan CardioVascular Institutue at Covenant Medical Center
Saginaw, Michigan, United States, 48602
Saint Joseph Mercy Hospital
Ypsilanti, Michigan, United States, 48197
United States, Minnesota
Abbott Northwestern Hospital / Minneapolis Heart Institute-Vascular Clinic
Minneapolis, Minnesota, United States, 55407
University of Minnesota Medical School
Minneapolis, Minnesota, United States, 55455
Minneapolis VA Health Care System
Minneapolis, Minnesota, United States, 55417
United States, Mississippi
Hattiesburg Clinic, P.A.
Hattiesburg, Mississippi, United States, 39401
United States, Missouri
Saint Luke's Hospital
Kansas City, Missouri, United States, 64111
United States, Nebraska
Omaha VAMC
Omaha, Nebraska, United States, 68105
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Vascular Access Center of West Orange
West Orange, New Jersey, United States, 07052
United States, New York
University of Buffalo Surgeons Inc.
Buffalo, New York, United States, 14203
Mount Sinai Medical Center
New York, New York, United States, 10029
Stony Brook University Medical Center
Stony Brook, New York, United States, 11794
United States, North Carolina
University of North Carolina Hospital
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
Jobst Vascular Institute
Toledo, Ohio, United States, 43606
University of Toledo Medical Center
Toledo, Ohio, United States, 43614
United States, Oklahoma
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
VA Pittsburgh Healthcare System
Pittsburgh, Pennsylvania, United States, 15240
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
Veterans' Administration Medical Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
United States, Texas
DFW Vascular Group, LLP
Dallas, Texas, United States, 75208
The Methodist Hospital
Houston, Texas, United States, 77030
Texas Heart Institute at St. Luke's Episcopal Hospital
Houston, Texas, United States, 77030
Audie L Murphy VA Hospital - Pathology Laboratory
San Antonio, Texas, United States, 78229
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Swedish Medical Center
Seattle, Washington, United States, 98122
University of Washington
Seattle, Washington, United States, 98195
Cascade Vascular Associates, P.S.
Tacoma, Washington, United States, 98405
United States, West Virginia
Charleston Area Medical Center - Memorial Hospital
Charleston, West Virginia, United States, 25304
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Wheaton Franciscan Medical Group, Inc.
Milwaukee, Wisconsin, United States, 53217
Columbia Saint Mary's
Milwaukee, Wisconsin, United States, 53211
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53203
Sponsors and Collaborators
Aastrom Biosciences
  More Information

Additional Information:
No publications provided

Responsible Party: Aastrom Biosciences
ClinicalTrials.gov Identifier: NCT01483898     History of Changes
Other Study ID Numbers: ABI 55-1009-1
Study First Received: November 30, 2011
Last Updated: July 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Aastrom Biosciences:
critical limb ischemia
REVIVE
peripheral vascular disease
CLI
PAD
MSC
stem cells
cell therapy

Additional relevant MeSH terms:
Ischemia
Pathologic Processes

ClinicalTrials.gov processed this record on August 28, 2014