Bone Marrow Aspirate Concentrate (BMAC) for Treatment of Critical Limb Ischemia (CLI)

• ClinicalTrials.gov Identifier: NCT01245335
• Recruitment Status: Completed
• First Posted: November 22, 2010
• Last Update Posted: December 15, 2015
• Sponsor: Harvest Technologies
• Information provided by (Responsible Party): Harvest Technologies

Study Description

Brief Summary:

Critical Limb Ischemia prevents the legs and feet from receiving oxygen and nutrients needed for proper function. This severe lack of blood flow can lead to painful legs while walking or at rest and can result in foot sores, ulcers, gangrene, and even amputation. The purpose of this study is to determine if injections of concentrated bone marrow into damaged tissues will result in improved blood flow. If successful, this treatment could improve blood flow to the lower limb, reduce pain, and reduce the frequency of limb amputations.

Condition or disease	Intervention/treatment	Phase
Critical Limb Ischemia	Device: BMAC injection; Device: Placebo injection	Phase 3

Detailed Description:

Bone marrow aspirate is collected and processed by centrifugation to remove red blood cells. The resulting concentrate of cells is injected into ischemic tissues of the lower limb. The purpose of this study is to determine if injections of concentrated bone marrow nucleated cells into ischemic tissues will result in vasculogenesis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Pivotal Study of the Safety and Effectiveness of Autologous Bone Marrow Aspirate Concentrate (BMAC) for the Treatment of Critical Limb Ischemia Due to Peripheral Arterial Disease
• Study Start Date: May 2011
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: November 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: BMAC Treatment; Intervention- Injection of 40 ml of autologous bone marrow concentrate (BMAC injection) prepared with the SmartPReP2 BMAC System	Device: BMAC injection; Injection of 40 ml of autologous bone marrow aspirate concentrate (BMAC injection) prepared with the SmartPReP2 BMAC System
Placebo Comparator: Placebo Injection; Injection of placebo (diluted peripheral blood) into ischemic tissue of the lower extremity	Device: Placebo injection; Injection of placebo into ischemic tissue of the lower extremity

Outcome Measures

Primary Outcome Measures :

1. Amputation Free Survival [ Time Frame: Six Months ]
   Survival without a major (above the ankle) amputation

Secondary Outcome Measures :

1. Change In Rutherford Classification [ Time Frame: Six Months ]
   Change in the subjects clinical status as measured by Rutherford Classification
2. Change in Pain [ Time Frame: Six Months ]
   Change in Subjects perception of pain as measured on a 100 mm visual analog scale

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient has Peripheral Arterial Occlusive Disease (PAOD) with clinical Rutherford Category 5 disease, as defined in the reporting standards adopted by the Society of Vascular Surgeons(table 1); Minor Tissue loss-focal gangrene with diffuse pedal ischemia

• Patient meets at least one of the following diagnostic criteria in the study limb:

  • Ankle artery occlusion pressure absolute ≤60 mmHg or ABI ≤0.6
  • Toe artery occlusive pressure < 50mm Hg or TBI ≤0.6

• There is no reasonable open surgical or endovascular revascularization option as determined by the treating vascular specialist. Factors that may contribute to the determination of inoperability may include:

  • Anatomical considerations
• No outflow targets
• No appropriate conduit (i.e. vein for bypass)

• Long segment occlusions or calcified lesions that predict poor outcome with endovascular approaches.

  • High risk medical conditions i.e. Unstable cardiac disease.
  • History of prior failed revascularization attempts
• The Patient's case was reviewed at the treating institution's Multidisciplinary Vascular Conference where the patient's status as a poor candidate for conventional therapies was confirmed.
• Age ≥18 years and ability to understand the planned treatment
• Subject has read and signed the IRB approved Informed Consent form
• Patients for whom the following medication(s) is prescribed must have a one month stable baseline therapy prior to enrollment: Plavix/asprin therapy, anticoagulation therapy, cholesterol lowering agent, and or blood pressure medication. If any of these medications are not prescribed notation of the reason for omission is to be provided.
• Hematocrit ≥ 28.0%, White Blood Cell count ≤ 14,000, Platelet count ≥ 50,000, Creatinine ≤ 2.5 mg / dL, INR ≤ 1.6 unless on Coumadin, or PTT <1.5 x control (to avoid bleeding complications) Patients on Coumadin will be corrected prior to the procedure and must have an INR<1.6 at the time of randomization/surgery.

Exclusion Criteria:

• Life expectancy <6 months due to concomitant illnesses
• History of bone marrow diseases (especially NHL, MDS) that prohibit transplantation
• Terminal renal failure with existing dependence on dialysis or serum creatinine >2.5 mg/dL
• Known active malignancy or results outside of normal limits from the following tests: PAP, Chest X-ray, PSA, Mammogram, Hemocult unless follow-up studies reveal patient to be cancer free.
• Poorly controlled diabetes mellitus (HgbA1C>10%)
• Medical risk that precludes anesthesia (conscious sedation), or ASA Class 5
• Life-threatening complications of the ischemia necessitating immediate amputation
• Uncorrected occlusion of the common or external iliac artery on index side
• Absence of any pulsatile Doppler flow below the ankle.
• Extensive necrosis of the index limb or other conditions that make amputation inevitable (Rutherford Category 6).
• Ulceration with exposed bone proximal to the distal metatarsal heads (ie. heel or mid foot)
• Active clinical infection or infection being treated by antibiotics within one week of enrollment
• Treatment with immunosuppressant drugs (including Prednisone > 5 mg per day).
• Female who is pregnant or nursing, or of child bearing potential and is not using a reliable birth control method.
• Underwent a major open cardiovascular surgical procedure (carotid endarterectomy, arterial aneurysm or bypass surgery, or coronary artery bypass surgery) or a myocardial infarction within the 3 months prior to randomization
• Underwent a successful or partially successful endovascular intervention for peripheral arterial occlusive disease. (ie. Aorta, iliac, femoral, popliteal, or tibial artery angioplasty, stenting, or atherectomy) within the prior 3 months.
• Endovascular coronary intervention (ie. Angioplasty, atherectomy, stenting) within 1 month prior to randomization.

• Underwent a failed attempt for endovascular revascularization during the prior 1 month. For the purpose of this exclusion criteria an endovascular procedure is considered a failure if:

  1. The procedure is diagnostic only with no intervention performed, (for example in the case where wire crossing can not be obtained).
  2. The treated artery recoils, thromboses, or dissects resulting in occlusion of the treated arterial segment, documented by intraoperative imaging. Note that endovascular procedures with suboptimal results but not meeting criteria 1 or 2 above may qualify for inclusion after 3 months as in #16 above.
• Cerebrovascular accident within 6 months prior to randomization.
• Treatment with topical growth factors or hyperbaric oxygen (HBO) within 30 days, or systemic growth factor treatment within 6 months of enrollment.
• Known hypersensitivity to heparin; or history of heparin-induced thrombocytopenia (HIT).

Contacts and Locations

  Hide Study Locations

Locations

United States, Alabama

University of Alabama

Birmingham, Alabama, United States, 35294-0012

United States, Arkansas

Medical Center of South Arkansas

El Dorado, Arkansas, United States, 71730

United States, California

USC Keck School of Medicine

Los Angeles, California, United States, 90033

United States, Florida

Florida Hospital - Vascular Institute of Central Florida

Orlando, Florida, United States, 32804

Coastal Vascular & Interventional

Pensacola, Florida, United States, 32503

USF / Tampa General

Tampa, Florida, United States, 33606

United States, Illinois

University of Illinois-Chicago

Chicago, Illinois, United States, 60612

Cadence Health, Central DuPage Hospital

Winfield, Illinois, United States, 60190

United States, Louisiana

Ochsner Clinic

New Orleans, Louisiana, United States, 70121

United States, Maine

Maine Medical Ctr

Portland, Maine, United States, 04102

United States, Maryland

Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Beth Israel Deaconess

Boston, Massachusetts, United States, 02215

United States, Missouri

Kansas City Vascular

Kansas City, Missouri, United States, 64116

Mercy Hospital

St. Louis, Missouri, United States, 63141

United States, New Hampshire

Dartmouth Hitchcock Medical Ctr

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Cooper University Hospital

Camden, New Jersey, United States, 08103

Holy Name Medical Center

Teaneck, New Jersey, United States, 07666

United States, New York

North Shore-Long Island Jewish

Lake Success, New York, United States, 11042

St. Luke's Roosevelt

New York, New York, United States, 10025

United States, North Carolina

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267

Regional Infectious Disease and Infusion Ctr

Lima, Ohio, United States, 45801

United States, Oklahoma

University of Oklahoma

Tulsa, Oklahoma, United States, 74135

United States, Oregon

Oregon Health Science University

Portland, Oregon, United States, 97239

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, South Carolina

Roper St Francis Medical Center

Charleston, South Carolina, United States, 29401

Greenville Health System

Greenville, South Carolina, United States, 29615

United States, Tennessee

University of Tennessee

Knoxville, Tennessee, United States, 37920

United States, Texas

Baylor Medical Ctr

Dallas, Texas, United States, 75226

University of Texas - Houston Medical School

Houston, Texas, United States, 77030

United States, Washington

Peace Health Southwest Medical Center

Vancouver, Washington, United States, 98682

United States, West Virginia

Charleston Area Medical Center Institute

Charleston, West Virginia, United States, 25304

Sponsors and Collaborators

Harvest Technologies

Investigators

• Principal Investigator: Mark Iafrati, MD; Tufts Medical Ctr

More Information

• Responsible Party: Harvest Technologies
• ClinicalTrials.gov Identifier: NCT01245335 History of Changes
• Other Study ID Numbers: CLI-2011-1
• First Posted: November 22, 2010
• Last Update Posted: December 15, 2015
• Last Verified: December 2015

Keywords provided by Harvest Technologies:

CLI; Critical Limb Ischemia; PAOD; Peripheral Arterial Disease; Stem Cells; Limb amputation; Leg ulcers

Additional relevant MeSH terms:

Peripheral Arterial Disease; Ischemia; Pathologic Processes; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases