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

Peripheral Arterial Disease Clinical Trial

— RESTORE-CLI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468000
• Other study ID #: ABI-55-0610-1
• Status: Completed
• Phase: Phase 2
• Start date: April 2007
• Est. completion date: March 2011

Study information

• Verified date: May 2020
• Source: Vericel Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Ischemia
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Biological:
• Ixmyelocel-T
IM injection
• Placebo
IM Injection

Locations

Country	Name	City	State
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	VA Ann Arbor Healthcare System	Ann Arbor	Michigan
United States	Cardiology, P.C.	Birmingham	Alabama
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	Michigan Vascular Research Center	Flint	Michigan
United States	Malcolm Randall Veterans Administration Medical Center, part of the North Florida/South Georgia Veterans Health System	Gainesville	Florida
United States	The Care Group, LLC	Indianapolis	Indiana
United States	Dartmouth-Hitchcock Memorial Center	Lebanon	New Hampshire
United States	Loyola University Stritch School of Medicine	Maywood	Illinois
United States	University of Miami/Miller School of Medicine	Miami	Florida
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Oklahoma University	Oklahoma City	Oklahoma
United States	Arizona Heart Institute	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Peripheral Vascular Associates	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Scott and White Hospital	Temple	Texas
United States	Jobst Vascular Center	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Vericel Corporation

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 au — View Citation

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; — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Percentage of patients failing treatment		Day 7, and Months 3,6,9, and 12
Secondary	Time to major amputation		Day 7 and Month 3, 6, 9, and 12
Secondary	Percentage of patients undergoing major amputation		Day 7 and Months 3, 6, 9, 12
Secondary	Incidence of revascularization interventions throughout duration of study		Day 7 and Months 3,6,9,12
Secondary	Incidence of bypass surgery for patients throughout duration of study		Day 7 and Months 3,6,9,12
Secondary	Healing of all wounds in the target limb		Day 7 and Months 3,6,9,12
Secondary	Ankle and/or toe pressure and ankle brachial pressure index and/or toe brachial index		Day 7 and Months 3,6,9,12
Secondary	Pain, as measured by visual analog scale(VAS)		Day 7 and Months 3,6,9,12
Secondary	The King's College Vascular Quality of Life Questionnaire		Baseline and Months 6 and 12
Secondary	Walking distance as measured by six-minute walk test(with or without walking device)		Baseline and Month 12
Secondary	Concurrent Meds for trends		Day 7 and Months 3, 6, 9, 12