Trial Design
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

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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.

Section snippets

Study objectives

The primary objectives of ENACT-AMI are to determine whether E-CMM therapy is effective and safe in improving cardiac function following acute MI, and whether endothelial nitric oxide synthase (eNOS) transfected E-CMMs are superior to non-transfected E-CMMs. A secondary objective is to determine whether the efficacy of E-CMM therapy depends on the timing of cell delivery (5-10 days vs 11-30 days post-MI).

Study design and setting

ENACT-AMI is a phase IIb, double-blind, parallel, randomized placebo-controlled trial, with

Discussion

ENACT-AMI will study the efficacy of cell therapy for acute MI using a cell manufacturing protocol that results in a population of well-characterized endothelial-like, culture modified MNCs (or early EPCs), which have been shown to have potent regenerative activity in lung vascular disease, hind limb ischemia and MI in preclinical models.17, 24, 25 To the best of our knowledge, this will be the first clinical trial to use gene-enhanced cell therapy for cardiac disease, by exploring the

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