Rationale and design of Enhanced Angiogenic Cell Therapy in Acute Myocardial Infarction (ENACT-AMI): The first randomized placebo-controlled trial of enhanced progenitor cell therapy for acute myocardial infarction
Received 16 July 2009; accepted 31 December 2009.
Background
Despite the widespread use of pharmacological and/or interventional reperfusion therapies, recovery of cardiac function in myocardial infarction (MI) patients is often modest or even absent. Unlike classical pharmacological treatments, the use of progenitor cells could potentially restore functional tissue in regions that otherwise would form only scar. However, a major limitation of autologous cell therapy is the deleterious influence of age and cardiac risk factors on progenitor cell activity.
Trial Design
The ENACT-AMI trial is a phase IIb, double-blind, randomized placebo-controlled trial, using transplantation of autologous early endothelial progenitor cells (EPCs) for patients who have suffered large MI. Circulating mononuclear cells (MNCs) are obtained by apheresis and subjected to differential culture for 3 days to select a population of highly regenerative, endothelial-like, culture modified MNCs (E-CMMs), often referred to as “early EPCs.” A total of 99 patients will be randomized to placebo (Plasma-Lyte A), autologous E-CMMs, or E-CMMs transfected with human endothelial nitric oxide synthase delivered by coronary injection into the infarct-related artery. The primary efficacy end point is change from baseline to 6 months in global left ventricular ejection fraction by cardiac MRI; secondary endpoints include regional wall motion, wall thickening, infarct volume, time to clinical worsening, and quality of life.
Conclusions
This will be the first clinical trial to include a strategy designed to enhance the function of autologous progenitor cells by overexpressing endothelial nitric oxide synthase, and the first to use combination gene and cell therapy for the treatment of cardiac disease.
aClinical Epidemiology Program, Ottawa Hospital Research Institute
bDepartment of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada
cInstitute of Medical Science, University of Toronto, Toronto, Canada
dDepartment of Cardiology, St Michael's Hospital, Toronto, Canada
eDepartment of Surgery, St. Michael's Hospital, University of Toronto
fClinical Research Administration, Ottawa Hospital Research Institute, Ottawa, Canada
gDivision of Cardiology, Canadian Heart Research Centre and Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Canada
hSunnybrook Health Sciences Centre, Toronto, Canada
iLady Davis Institute for Medical Research and Division of Hematology/Oncology, Jewish General Hospital, Montreal, Canada
jOttawa Hospital Research Institute; Department of Medicine, University of Ottawa, Ottawa, Canada
Reprint requests: Monica Taljaard, PhD, Ottawa Hospital Research Institute Clinical Epidemiology Program Ottawa Hospital, Civic Campus 1053 Carling Avenue, C409 Ottawa, ON, Canada K1Y 4E9.
ABSTRACT