Clinical trial NCT01483898: An Efficacy and Safety Study of Ixmyelocel-T in Patients With Critical Limb Ischemia (CLI)
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study To Evaluate The Efficacy, Safety, And Tolerability Of Ixmyelocel-T In Subjects With Critical Limb Ischemia And No Options For Revascularization
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Critical Limb Ischemia
Keywords: critical limb ischemia
REVIVE
peripheral vascular disease
CLI
PAD
MSC
stem cells
cell therapy
Lead sponsor: Vericel Corporation
Sponsor class: INDUSTRY
First posted: 2011-12-02
Enrollment: 41
Sex: ALL
Minimum age (years): 35
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 efficacy and safety of ixmyelocel-T, a patient-specific expanded multicellular therapy, for the treatment of patients with critical limb ischemia (CLI). The study is a randomized, vehicle controlled (placebo)study in CLI patients who have no option for revascularization procedures. All patients randomized will undergo a small volume bone marrow aspiration in a 15-minute outpatient or in-office procedure. All patients will receive injections of either ixmyelocel-T or vehicle-control into their pre-identified index leg. Patients will be followed for 18 months.


Eligibility criteria: Inclusion Criteria:

* Males and nonpregnant, nonlactating females
* Ages 35 to 90 years of age
* Diagnosis of CLI with tissue loss (corresponding to Rutherford Category 5; see Appendix B) having an ulcer size of at least 0.5 cm2, a smaller sized ulcer penetrating into the subcutaneous tissue, and/or gangrene (dry). In addition, the subject must have ONE of the following documented at screening:

  * Ankle systolic pressure \< 70 mm Hg
  * Toe systolic pressure \< 50 mm Hg
  * TcPO2 \< 30 mm Hg (in a supine position)
* Subjects must have no reasonable standard-of-care options for surgical or endovascular revascularization interventions
* Subjects must have the following:

  * A narrative documenting the reasons why the site vascular specialist considers the subject "no option". A vascular specialist will be the principal investigator (PI) or subinvestigator and is defined as: vascular surgeon, interventional cardiologist, certified vascular medicine specialist, or interventional radiologist; AND
  * Secondary confirmation by an independent Eligibility Review Committee (ERC; see Section 8.1) after review of appropriate documents including, but not limited to: imaging results, medical records, surgical history, site vascular specialist narrative documenting reasons for "no option," and/or lab reports.
* Major amputation in the index leg or death is not anticipated within 3 months of screening in the opinion of the vascular specialist (who must be the PI or subinvestigator)
* In the opinion of the investigator, the subject is controlled on medical therapy indicated for CLI (unless there is a documented contraindication or intolerance)
* Subject is current with all age-appropriate American Cancer Society (ACS) or similar (e.g., United States Preventative Service Task Force) screening guidelines
* Given medical history and concurrent medication, the subject is an acceptable candidate for bone marrow aspiration and intramuscular injection procedures in the opinion of the Investigator
* Subject is willing and able to comply with the scheduled visits, aspiration/injection procedure, wound care instructions treatment plan, and other study procedures for the duration of the study
* Provide a personally-signed and dated informed consent document indicating that the subject (or a legally-acceptable representative, if permitted by the site's Investigational Review Board \[IRB\]) has been informed of all pertinent aspects of the study

Exclusion Criteria:

Patients presenting with any of the following will not be randomized:

Disease-specific:

* Failed open surgical revascularization (on index leg) within 4 weeks of screening Visit 1
* Acute limb-threatening ischemia, trauma, known non-atherosclerotic vascular disease (e.g., temporal/giant cell arteritis, Takayasu's arteritis, Raynaud's occlusive disease, Buerger's disease), embolic disease, aortoiliac disease with \> 50% stenosis, or history of hypercoagulable states
* Advanced CLI (i.e., nonsalvageable) defined as Rutherford Category 6
* Clinical evidence of invasive infection in index leg (e.g., cellulitis, osteomyelitis, wet gangrene)
* At screening, non-heel wound size of \> 20 cm2 (excluding toe gangrene); or wounds on the heel \> 10 cm2 on the index leg as measured by the Wound Core Lab (WCL) from photographs (and/or acetates) provided by the site
* Previous amputation at or above the talus in the index leg Medical History
* Hemoglobin A1c (HbA1c) ≥ 10% at screening
* Diabetic subjects with uncontrolled or untreated proliferative retinopathy as determined by dilated eye exam (by qualified eye care professional as per American Diabetes Association guidelines)
* Blood clotting disorder not caused by medication (e.g., thrombophilia)
* Active non-basal cell cutaneous malignancy requiring surgery, chemotherapy, and/or radiation in the past 12 months
* Current documented drug or alcohol abuse that would interfere with the subject's compliance with study procedures
* Known allergies to any equine, porcine, or bovine products
* Body mass index (BMI) ≥ 50 kg/m2 at screening
* Established chronic kidney disease (CKD) requiring dialysis (Stage 5); estimated creatinine clearance \< 15 mg/mL/min at screening
* Systolic blood pressure (SBP) \> 200 mm Hg or diastolic blood pressure (DBP) \> 120 mm Hg or papilledema noted via ophthalmoscope at screening physical exam
* Within 3 months prior to screening, a clinically significant history of cardiac disease

Laboratory Parameters:

* Abnormal laboratory values (performed at central lab) at screening:

  * Platelets \< 50,000 μL
  * Aspartate aminotransferase/alanine aminotransferase (AST/ALT) \> 3 times the upper limit of normal (ULN)
  * Human immunodeficiency virus 1 (HIV 1), HIV 2, or syphilis positive (rapid plasma reagin \[RPR\])
  * Active hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV); Exclusionary Procedures, Devices, or Medication
* Exposure to immunosuppressive therapy for oncologic or chronic non-oncologic reasons in the prior 12 months or expected requirement over the course of the study (e.g., chemotherapy, radiation therapy, methotrexate)
* Concurrent participation in another clinical trial or receiving experimental medication within 30 days of screening or having previously been exposed to Aastrom's ixmyelocel T product \[previously known as tissue repair cells (TRC), cardiac repair cells (CRC), vascular repair cells (VRC)\]
* On the index leg, use of concomitant wound treatments not currently approved for ischemic wound-healing within 30 days prior to screening or plans to initiate new, nonstandard-of-care treatments to the index leg during the study

Primary outcomes:
measure: Amputation free survival (AFS) at 12 months post-injection
timeFrame: 12 months
Secondary outcomes:
measure: Percent of patients with adverse events
timeFrame: 18 months
measure: Percent of patients with complete wound closure by Month 12
timeFrame: 12 months
measure: Percent of patients experiencing a major cardiac event (MACE) by Months 6, 12, and 18
timeFrame: 6, 12 and 18 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology PC
state: Alabama
city: Birmingham
country: United States
facility: Cardio-Thoracic Surgeons, P.C.
state: Alabama
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Heart Institute
state: Arizona
city: Phoenix
country: United States
facility: Carl T. Hayden VA Medical Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic, P.A.
state: Arkansas
city: Little Rock
country: United States
facility: Central Arkansas Veteran's Healthcare System
state: Arkansas
city: Concord
country: United States
facility: John Muir Medical Center - Concord Campus
state: California
city: Loma Linda
country: United States
facility: VA Loma Linda Healthcare
state: California
city: Los Angeles
country: United States
facility: UCLA Gonda Venous Center & Ambulatory Procedure Unit
state: California
city: Sacramento
country: United States
facility: Sutter Medical Group - Cardiology
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco - Division of Vascular and Endovascular Surgery
state: California
city: Aurora
country: United States
facility: University of Colorado Denver - Anschutz Medical Campus
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Boynton Beach
country: United States
facility: Bethesda Memorial Hospital - Clinical Research Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: Florida Research Network, LLC
state: Florida
city: Gainesville
country: United States
facility: Malcom Randall Veterans Affairs Medical Center
state: Florida
city: Jacksonville
country: United States
facility: First Coast Cardiovascular Institute, P.A.
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Pensacola
country: United States
facility: Baptist Hospital
state: Florida
city: Pensacola
country: United States
facility: Cardiology Consultants
state: Florida
city: Vero Beach
country: United States
facility: Grove Place Surgery Center
state: Florida
city: Marietta
country: United States
facility: Vascular Surgical Associates, P.C.
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago - Clinical Sciences North
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Indiana/Ohio Heart
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Medical Group, Inc.
state: Indiana
city: Windsor Heights
country: United States
facility: Heartland Vascular Medicine and Surgery
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Clinic foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Union Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Memorial Health Care
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: Berkley
country: United States
facility: Cardiology and Vascular Associates, P.C.
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: John D. Dingell VA Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: Michigan Vascular Research Center
state: Michigan
city: Grand Blanc
country: United States
facility: Integrated Vascular Vein Center of Michigan
state: Michigan
city: Saginaw
country: United States
facility: Michigan CardioVascular Institutue at Covenant Medical Center
state: Michigan
city: Ypsilanti
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital / Minneapolis Heart Institute-Vascular Clinic
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic, P.A.
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Omaha
country: United States
facility: Omaha VAMC
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: West Orange
country: United States
facility: Vascular Access Center of West Orange
state: New Jersey
city: Buffalo
country: United States
facility: University of Buffalo Surgeons Inc.
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Toledo
country: United States
facility: Jobst Vascular Institute
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Veterans' Administration Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: DFW Vascular Group, LLP
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute at St. Luke's Episcopal Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Audie L Murphy VA Hospital - Pathology Laboratory
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Tacoma
country: United States
facility: Cascade Vascular Associates, P.S.
state: Washington
city: Charleston
country: United States
facility: Charleston Area Medical Center - Memorial Hospital
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia Saint Mary's
state: Wisconsin
city: Milwaukee
country: United States
facility: Wheaton Franciscan Medical Group, Inc.
state: Wisconsin
Study officials:
References: