Clinical trial NCT00468000: Use of Ixmyelocel-T (Formerly Vascular Repair Cells [VRC]) in Patients With Peripheral Arterial Disease to Treat Critical Limb Ischemia
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral Arterial Disease
Keywords: Peripheral Arterial Disease
Critical Limb Ischemia
Ischemia
Peripheral Vascular Disease
ixmyelocel-T
Lead sponsor: Vericel Corporation
Sponsor class: INDUSTRY
First posted: 2007-05-01
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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)
timeFrame: throughout trial
Secondary outcomes:
measure: Composite efficacy endpoint assessing time to treatment failure(failure defined as major amputation, doubling of wound size, and new gangrene)
timeFrame: Day 7 and Months 3, 6, 9, 12
measure: Percentage of patients failing treatment
timeFrame: Day 7, and Months 3,6,9, and 12
measure: Time to major amputation
timeFrame: Day 7 and Month 3, 6, 9, and 12
measure: Percentage of patients undergoing major amputation
timeFrame: Day 7 and Months 3, 6, 9, 12
measure: Incidence of revascularization interventions throughout duration of study
timeFrame: Day 7 and Months 3,6,9,12
measure: Incidence of bypass surgery for patients throughout duration of study
timeFrame: Day 7 and Months 3,6,9,12
measure: Healing of all wounds in the target limb
timeFrame: Day 7 and Months 3,6,9,12
measure: Ankle and/or toe pressure and ankle brachial pressure index and/or toe brachial index
timeFrame: Day 7 and Months 3,6,9,12
measure: Pain, as measured by visual analog scale(VAS)
timeFrame: Day 7 and Months 3,6,9,12
measure: The King's College Vascular Quality of Life Questionnaire
timeFrame: Baseline and Months 6 and 12
measure: Walking distance as measured by six-minute walk test(with or without walking device)
timeFrame: Baseline and Month 12
measure: Concurrent Meds for trends
timeFrame: Day 7 and Months 3, 6, 9, 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology, P.C.
state: Alabama
city: Phoenix
country: United States
facility: Arizona Heart Institute
state: Arizona
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Gainesville
country: United States
facility: Malcolm Randall Veterans Administration Medical Center, part of the North Florida/South Georgia Veterans Health System
state: Florida
city: Miami
country: United States
facility: University of Miami/Miller School of Medicine
state: Florida
city: Maywood
country: United States
facility: Loyola University Stritch School of Medicine
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: The Care Group, LLC
state: Indiana
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Flint
country: United States
facility: Michigan Vascular Research Center
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Memorial Center
state: New Hampshire
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Toledo
country: United States
facility: Jobst Vascular Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: San Antonio
country: United States
facility: Peripheral Vascular Associates
state: Texas
city: Temple
country: United States
facility: Scott and White Hospital
state: Texas
Study officials:
affiliation: Jobst Vascular Center
name: Anthony J Comerota, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.