Clinical trial NCT01049919: Safety and Efficacy Study of Autologous Concentrated Bone Marrow Aspirate (cBMA) for Critical Limb Ischemia (CLI)
Official title: MarrowStim PAD Kit for the Treatment of Critical Limb Ischemia (CLI) in Subjects With Severe Peripheral Arterial Disease (PAD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Critical Limb Ischemia
Peripheral Arterial Disease
Peripheral Vascular Disease
Keywords: Critical Limb Ischemia
Peripheral Arterial Disease
Peripheral Vascular Disease
CLI
PAD
PVD
Angiogenesis
Stem Cells
Cell Therapy
Limb Salvage
Amputation
Leg Pain
Lead sponsor: Zimmer Biomet
Sponsor class: INDUSTRY
First posted: 2010-01-15
Enrollment: 153
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will evaluate the safety and efficacy of concentrated bone marrow aspirate (cBMA) to prevent or delay major amputation and/or death in subjects with critical limb ischemia (CLI) due to severe peripheral arterial disease (PAD).

Detailed description: This is a prospective, randomized, double-blind, placebo controlled, multicenter trial intended for subjects with critical limb ischemia (CLI) that are unsuitable for revascularization. The investigational treatment utilizes autologous concentrated bone marrow aspirate (cBMA) at the point of care. The bone marrow aspirate is obtained from the subject's hip, concentrated with a bone marrow concentration device, and delivered intramuscularly to the affected limb. Subjects meeting the inclusion/exclusion criteria will be randomized to receive either the investigational treatment (cBMA) or a placebo control (sham treatment).

Eligibility criteria: Inclusion Criteria:

* Unilateral or bilateral lower extremity ischemia due to advanced peripheral arterial disease
* Unsuitable for revascularization
* Minor tissue loss (Rutherford Category 5) or ischemic rest pain (Rutherford Category 4) with ABI ≤ 0.6, or TBI ≤ 0.4, or TcPO2 ≤ 50 mm Hg
* Competent to give consent
* No current malignancy or history of previous malignancy within the last five years, with the exception of adequately treated non-melanoma skin cancer (evidence of standard preventative cancer screenings required)

Exclusion Criteria:

* Major tissue loss (Rutherford Category 6)
* Diabetics on oral or insulin therapy with uncontrolled or untreated proliferative retinopathy (evidence of retinal exam required)
* Poorly controlled diabetes mellitus with HbA1C \> 10% (evidence of HbA1C test required)
* Uncompensated congestive heart failure (New York Heart Association Class IV) and/or other conditions that preclude general anesthesia
* Myocardial infarction or stroke within last 90 days
* Elevated liver function tests (AST or ALT more than twice normal upper limit)
* Renal disease (creatinine \> 2.5 mg/dl) or chronic hemodialysis
* White blood cell count \< 3,000/µL or \> 15,000/µL, platelet count \< 100,000/µL, or hematocrit \< 32%
* Topical growth hormone therapy within last 90 days, or injected growth hormone therapy within last 180 days
* Disease of central nervous system and/or other conditions that impair cognitive function
* Two or more episodes of pulmonary embolus with a documented DVT in index leg or history of DVT in index leg without evidence of clot resolution
* Current infection of index leg
* Pregnant women (negative urine pregnancy test required)
* Lower extremity venous disease with pitting edema in index leg
* Recent history (in the 6 months prior to screening) of bone marrow disease or treatment with any medication or procedure which adversely affects the bone marrow and would prohibit transplantation
* Current osteomyelitis in index leg
* Existing HIV diagnosis
* Organ transplant recipients
* Known terminal disease process with life expectancy less than one year
* Severe concomitant disease(s) or any additional condition(s) which the investigator feels constitute(s) criteria for exclusion of a particular subject
* Major amputation required within 30 days
* Inclusion in any other clinical study that may affect the outcome of this study
* Uncorrected stenosis(es) of greater than 50% in the common and/or external iliac artery and/or common femoral artery of the index leg.

Primary outcomes:
measure: Occurrence of Major Amputation or Death
timeFrame: 52 weeks
Secondary outcomes:
measure: Visual Analog Scale (VAS) - Pain
timeFrame: 52 weeks
measure: Six-Minute Walk Test
timeFrame: 52 weeks
Other outcomes:
measure: Occurrence of Major Amputation or Death
timeFrame: 5 years
Locations:
city: Little Rock
country: United States
facility: Central Arkansas Veterans Healthcare System
state: Arkansas
city: Sacramento
country: United States
facility: University of California-Davis Medical Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Health Care
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Omaha
country: United States
facility: Nebraska-Western Iowa VA Healthcare System
state: Nebraska
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College / New York-Presbyterian Hospital
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Remington-Davis
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System
state: Pennsylvania
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Hospital
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Indiana University School of Medicine
name: Michael P. Murphy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Murphy MP, Lawson JH, Rapp BM, Dalsing MC, Klein J, Wilson MG, Hutchins GD, March KL. Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia. J Vasc Surg. 2011 Jun;53(6):1565-74.e1. doi: 10.1016/j.jvs.2011.01.074. Epub 2011 Apr 22.