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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)

Primary Purpose

Peripheral Arterial Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ixmyelocel-T
Placebo
Sponsored by
Vericel Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Arterial Disease focused on measuring Peripheral Arterial Disease, Critical Limb Ischemia, Ischemia, Peripheral Vascular Disease, ixmyelocel-T

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cardiology, P.C.
  • Arizona Heart Institute
  • University of California, San Francisco
  • Malcolm Randall Veterans Administration Medical Center, part of the North Florida/South Georgia Veterans Health System
  • University of Miami/Miller School of Medicine
  • Loyola University Stritch School of Medicine
  • Southern Illinois University School of Medicine
  • The Care Group, LLC
  • VA Ann Arbor Healthcare System
  • St. Joseph Mercy Hospital
  • Michigan Vascular Research Center
  • Minneapolis Heart Institute Foundation
  • Dartmouth-Hitchcock Memorial Center
  • University of North Carolina Hospitals
  • Jobst Vascular Center
  • Oklahoma University
  • University of Pittsburgh Medical Center
  • Vanderbilt University Medical Center
  • Peripheral Vascular Associates
  • Scott and White Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ixmyelocel-T

Placebo

Arm Description

The treatment arm of the study will receive injections of the study cellular product.

The control arm of the study will receive placebo injections.

Outcomes

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)

Secondary Outcome Measures

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

Full Information

First Posted
April 30, 2007
Last Updated
May 18, 2020
Sponsor
Vericel Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00468000
Brief Title
Use of Ixmyelocel-T (Formerly Vascular Repair Cells [VRC]) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vericel Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Arterial Disease
Keywords
Peripheral Arterial Disease, Critical Limb Ischemia, Ischemia, Peripheral Vascular Disease, ixmyelocel-T

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
86 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ixmyelocel-T
Arm Type
Experimental
Arm Description
The treatment arm of the study will receive injections of the study cellular product.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The control arm of the study will receive placebo injections.
Intervention Type
Biological
Intervention Name(s)
Ixmyelocel-T
Intervention Description
IM injection
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
IM Injection
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
Percentage of patients failing treatment
Time Frame
Day 7, and Months 3,6,9, and 12
Title
Time to major amputation
Time Frame
Day 7 and Month 3, 6, 9, and 12
Title
Percentage of patients undergoing major amputation
Time Frame
Day 7 and Months 3, 6, 9, 12
Title
Incidence of revascularization interventions throughout duration of study
Time Frame
Day 7 and Months 3,6,9,12
Title
Incidence of bypass surgery for patients throughout duration of study
Time Frame
Day 7 and Months 3,6,9,12
Title
Healing of all wounds in the target limb
Time Frame
Day 7 and Months 3,6,9,12
Title
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
Title
Pain, as measured by visual analog scale(VAS)
Time Frame
Day 7 and Months 3,6,9,12
Title
The King's College Vascular Quality of Life Questionnaire
Time Frame
Baseline and Months 6 and 12
Title
Walking distance as measured by six-minute walk test(with or without walking device)
Time Frame
Baseline and Month 12
Title
Concurrent Meds for trends
Time Frame
Day 7 and Months 3, 6, 9, 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony J Comerota, MD
Organizational Affiliation
Jobst Vascular Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cardiology, P.C.
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35211
Country
United States
Facility Name
Arizona Heart Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Malcolm Randall Veterans Administration Medical Center, part of the North Florida/South Georgia Veterans Health System
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
University of Miami/Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Loyola University Stritch School of Medicine
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Southern Illinois University School of Medicine
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
The Care Group, LLC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
VA Ann Arbor Healthcare System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
St. Joseph Mercy Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Michigan Vascular Research Center
City
Flint
State/Province
Michigan
ZIP/Postal Code
48507
Country
United States
Facility Name
Minneapolis Heart Institute Foundation
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Dartmouth-Hitchcock Memorial Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
University of North Carolina Hospitals
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Jobst Vascular Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
Oklahoma University
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2735
Country
United States
Facility Name
Peripheral Vascular Associates
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78205
Country
United States
Facility Name
Scott and White Hospital
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22453769
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;20(6):1280-6. doi: 10.1038/mt.2012.52. Epub 2012 Mar 27.
Results Reference
result
PubMed Identifier
21684715
Citation
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.
Results Reference
result
PubMed Identifier
35802393
Citation
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.
Results Reference
derived

Learn more about this trial

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

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