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Use of Ixmyelocel-T (Formerly Vascular Repair Cells [VRC]) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia (RESTORE-CLI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Aastrom Biosciences
ClinicalTrials.gov Identifier:
NCT00468000
First received: April 30, 2007
Last updated: October 1, 2012
Last verified: October 2012
  Purpose

This study is designed to evaluate the safety and efficacy of autologous Vascular Repair Cells (VRC) for patients with peripheral arterial disease as a treatment for critical limb ischemia.

The double-blind study is expected to enroll 150 patients, randomized into two patient groups. The treatment group will receive intramuscular (IM) injections of the VRCs into the affected limb; the control group will receive intramuscular injections with an electrolyte solution (without cells). Both groups will receive the standard of care appropriate for their medical condition.


Condition Intervention Phase
Peripheral Arterial Disease
Biological: autologous bone marrow cells
Biological: electrolyte solution (without cells)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Use of Ixmyelocel-T (Formerly TRC Autologous Bone Marrow Cells) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia

Resource links provided by NLM:


Further study details as provided by Aastrom Biosciences:

Primary Outcome Measures:
  • Safety of TRCs in patients with CLI(key safety parameters include vital signs, physical exams, laboratory results, assessment of aspiration and injection sites, adverse events, major amputations, wounds presence(size and grading using the Wagner scale) [ Time Frame: throughout trial ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Composite efficacy endpoint assessing time to treatment failure(failure defined as major amputation, doubling of wound size, and new gangrene) [ Time Frame: Day 7 and Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
  • Percentage of patients failing treatment [ Time Frame: Day 7, and Months 3,6,9, and 12 ] [ Designated as safety issue: No ]
  • Time to major amputation [ Time Frame: Day 7 and Month 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
  • Percentage of patients undergoing major amputation [ Time Frame: Day 7 and Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
  • Incidence of revascularization interventions throughout duration of study [ Time Frame: Day 7 and Months 3,6,9,12 ] [ Designated as safety issue: No ]
  • Incidence of bypass surgery for patients throughout duration of study [ Time Frame: Day 7 and Months 3,6,9,12 ] [ Designated as safety issue: No ]
  • Healing of all wounds in the target limb [ Time Frame: Day 7 and Months 3,6,9,12 ] [ Designated as safety issue: No ]
  • Ankle and/or toe pressure and ankle brachial pressure index and/or toe brachial index [ Time Frame: Day 7 and Months 3,6,9,12 ] [ Designated as safety issue: No ]
  • Pain, as measured by visual analog scale(VAS) [ Time Frame: Day 7 and Months 3,6,9,12 ] [ Designated as safety issue: No ]
  • The King's College Vascular Quality of Life Questionnaire [ Time Frame: Baseline and Months 6 and 12 ] [ Designated as safety issue: No ]
  • Walking distance as measured by six-minute walk test(with or without walking device) [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
  • Concurrent Meds for trends [ Time Frame: Day 7 and Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]

Enrollment: 86
Study Start Date: April 2007
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
The Treatment arm of the study will receive standard of care therapy and injections of the study cellular product.
Biological: autologous bone marrow cells
IM injection
Other Name: Vascular Repair Cells (VRCs)
Placebo Comparator: Control
The Control arm of the study will receive standard of care and placebo injections.
Biological: electrolyte solution (without cells)
IM Injection

Detailed Description:

The study will assess the safety and ability of Aastrom TRC autologous bone marrow cells to restore peripheral blood flow affected by critical limb ischemia.

Peripheral arterial disease (PAD), also known as Peripheral Vascular Disease (PVD), occurs when peripheral arteries are damaged by arterial hypertension and/or by the formation of atherosclerotic plaques. PAD is a chronic disease that progressively constricts arterial circulation of limbs. The term critical limb ischemia (CLI) is used for all patients with chronic ischemia rest pain, ulcers, or gangrene in limbs attributable to objectively proven PAD. These sequelae represent the end stage of PAD. PAD is associated with several other clinical conditions, i.e. hypertension, cardiovascular disease, hyperlipidemia, diabetes, tobacco use, obesity and stroke.

The double-blind study is expected to enroll 150 patients, randomized into two patient groups. The treatment group will receive intramuscular injections of the TRC product into the affected limb; the control group will receive intramuscular injections with an electrolyte solution (without cells). Both groups will receive the standard of care appropriate for their medical condition.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females, 18-90 years of age
  • Diagnosis of CLI
  • Infrainguinal occlusive disease, without options for revascularization
  • No surgical interventions planned
  • Life expectancy of 2 years
  • Normal organ and marrow function
  • Patients with controlled blood pressure (≤ 180/110 mmHg) and established anti-hypertensive therapy
  • Established anti-platelet therapy

Exclusion Criteria:

  • Poorly controlled diabetes mellitus (hemoglobin A1c [HbA1c] > 10%)
  • Aortoiliac disease with > 50% stenosis
  • Wounds with severity greater than Grade 3 on the Wagner Scale
  • Any known failed ipsilateral revascularization within 2 weeks of enrollment
  • Previous amputation of the talus, or above in the target limb
  • Life-threatening ventricular arrhythmia; unstable angina; or, myocardial infarction within 4 weeks of enrollment
  • Severe congestive heart failure (CHF) (i.e. New York Heart Association [NYHA] Stage IV)
  • Receiving treatment with hematopoietic growth factors
  • Infection of the involved extremity(ies)
  • Active wet gangrenous tissue
  • Require uninterruptible anticoagulation therapy
  • Blood clotting disorder
  • Cancer
  • End stage renal disease requiring dialysis for more than 6 months prior to enrollment
  • Pregnant or lactating
  • Having received medication for thrombolytic therapy (e.g. rTPA or other enzymatic clot busters) within 30 days prior to enrollment
  • Undergoing hyperbaric oxygen treatment within 2 weeks of enrollment
  • Concomitant wound treatments with growth factors or tissue engineered products
  • Receiving anti-angiogenic drugs
  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: NCT00468000

Locations
United States, Alabama
Cardiology, P.C.
Birmingham, Alabama, United States, 35211
United States, Arizona
Arizona Heart Institute
Phoenix, Arizona, United States, 85006
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Florida
Malcolm Randall Veterans Administration Medical Center, part of the North Florida/South Georgia Veterans Health System
Gainesville, Florida, United States, 32608
University of Miami/Miller School of Medicine
Miami, Florida, United States, 33136
United States, Illinois
Loyola University Stritch School of Medicine
Maywood, Illinois, United States, 60153
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62702
United States, Indiana
The Care Group, LLC
Indianapolis, Indiana, United States, 46260
United States, Michigan
St. Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, United States, 48105
Michigan Vascular Research Center
Flint, Michigan, United States, 48507
United States, Minnesota
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States, 55407
United States, New Hampshire
Dartmouth-Hitchcock Memorial Center
Lebanon, New Hampshire, United States, 03756
United States, North Carolina
University of North Carolina Hospitals
Chapel Hill, North Carolina, United States, 27514
United States, Ohio
Jobst Vascular Center
Toledo, Ohio, United States, 43606
United States, Oklahoma
Oklahoma University
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-2735
United States, Texas
Peripheral Vascular Associates
San Antonio, Texas, United States, 78205
Scott and White Hospital
Temple, Texas, United States, 76508
Sponsors and Collaborators
Aastrom Biosciences
Investigators
Principal Investigator: Anthony J Comerota, MD Jobst Vascular Center
  More Information

Publications:
Responsible Party: Aastrom Biosciences
ClinicalTrials.gov Identifier: NCT00468000     History of Changes
Other Study ID Numbers: ABI-55-0610-1
Study First Received: April 30, 2007
Last Updated: October 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Aastrom Biosciences:
Peripheral Arterial Disease
Critical Limb Ischemia
Ischemia
Peripheral Vascular Disease
ixmyelocel-T

Additional relevant MeSH terms:
Ischemia
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014