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

Use of Ixmyelocel-T (Formerly TRC Autologous Bone Marrow Cells) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Biological: Ixmyelocel-T; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ixmyelocel-T; The treatment arm of the study will receive injections of the study cellular product.	Biological: Ixmyelocel-T; IM injection
Placebo Comparator: Placebo; The control arm of the study will receive placebo injections.	Biological: Placebo; IM Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)	throughout trial

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite efficacy endpoint assessing time to treatment failure(failure defined as major amputation, doubling of wound size, and new gangrene)	Day 7 and Months 3, 6, 9, 12
Percentage of patients failing treatment	Day 7, and Months 3,6,9, and 12
Time to major amputation	Day 7 and Month 3, 6, 9, and 12
Percentage of patients undergoing major amputation	Day 7 and Months 3, 6, 9, 12
Incidence of revascularization interventions throughout duration of study	Day 7 and Months 3,6,9,12
Incidence of bypass surgery for patients throughout duration of study	Day 7 and Months 3,6,9,12
Healing of all wounds in the target limb	Day 7 and Months 3,6,9,12
Ankle and/or toe pressure and ankle brachial pressure index and/or toe brachial index	Day 7 and Months 3,6,9,12
Pain, as measured by visual analog scale(VAS)	Day 7 and Months 3,6,9,12
The King's College Vascular Quality of Life Questionnaire	Baseline and Months 6 and 12
Walking distance as measured by six-minute walk test(with or without walking device)	Baseline and Month 12
Concurrent Meds for trends	Day 7 and Months 3, 6, 9, 12

Collaborators and Investigators

• Sponsor: Vericel Corporation
• Investigators: Principal Investigator: Anthony J Comerota, MD, Jobst Vascular Center

Publications and helpful links

General Publications

• Moazzami B, Mohammadpour Z, Zabala ZE, Farokhi E, Roohi A, Dolmatova E, Moazzami K. Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia. Cochrane Database Syst Rev. 2022 Jul 8;7(7):CD008347. doi: 10.1002/14651858.CD008347.pub4.
• Powell RJ, Marston WA, Berceli SA, Guzman R, Henry TD, Longcore AT, Stern TP, Watling S, Bartel RL. Cellular therapy with Ixmyelocel-T to treat critical limb ischemia: the randomized, double-blind, placebo-controlled RESTORE-CLI trial. Mol Ther. 2012 Jun;20(6):1280-6. doi: 10.1038/mt.2012.52. Epub 2012 Mar 27.
• Powell RJ, Comerota AJ, Berceli SA, Guzman R, Henry TD, Tzeng E, Velazquez O, Marston WA, Bartel RL, Longcore A, Stern T, Watling S. Interim analysis results from the RESTORE-CLI, a randomized, double-blind multicenter phase II trial comparing expanded autologous bone marrow-derived tissue repair cells and placebo in patients with critical limb ischemia. J Vasc Surg. 2011 Oct;54(4):1032-41. doi: 10.1016/j.jvs.2011.04.006. Epub 2011 Jul 31.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: April 30, 2007
• First Submitted That Met QC Criteria: April 30, 2007
• First Posted (Estimate): May 1, 2007

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Peripheral Vascular Disease; Ischemia; Peripheral Arterial Disease; Critical Limb Ischemia; ixmyelocel-T
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: ABI-55-0610-1