The Enhanced Angiogenic Cell Therapy - Acute Myocardial Infarction Trial (ENACT-AMI)

• Assessment of Global LVEF [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  1. A change in global left ventricular ejection fraction by cardiac MRI between those treated with cell/gene enriched EPCs versus placebo
  2. Change in global left ventricular ejection fraction by cardiac MRI between those treated with non-transfected autologous EPCs versus eNOS transfected EPCs.
  
  

• Assessment of: Cardiac wall motion and volumes [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  1. Change in regional wall motion and regional wall thickening by cardiac MRI between the above patient groups
  2. Change in echocardiographic assessment of LVEF, infarct size and ventricular volumes between the above patient groups
  
  
• Time To Clinical Worsening (TTCW) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  Quality of Life Measures: Participants will complete SF-36 and DASI questionnaires at baseline, 3 and 6 months.
  
  
• Safety Measurements [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: Yes ]
  1. Clinically significant changes in CK and troponin more than 24 hours post delivery
  2. Clinically significant changes in ECG
  3. Assessment of major acute cardiac events
  4. Evidence of any systemic embolization during the hospitalization period
  5. Need for revacularization procedures
  
  

Introduction:

• Despite the widespread use of pharmacological and/or interventional reperfusion therapies, recovery of cardiac function in myocardial infarction patients is often modest or in some cases absent. Unlike classical re-perfusion therapies, which must be delivered before irreversible cardiac damage has occurred, the use of progenitor cells could potentially restore functional tissue in regions that otherwise would form only scar. A number of clinical trials have been performed, mainly using autologous bone marrow cells, and these suggest a significant albeit modest improvement in cardiac function post MI. However, a major limitation of autologous cell therapy in patients with cardiovascular disease is the deleterious influence of age and other cardiac risk factors on progenitor cell activity, which may limit greatly the potential efficacy of this promising approach.

Trial Design:

• The Enhanced Angiogenic Cell Therapy - Acute Myocardial Infarction (ENACT-AMI) trial is a Canadian, 5-center, phase IIb, double-blind, parallel, randomized placebo controlled trial assessing the safety and efficacy of cell and gene therapy for patients with moderate to large anterior STEMI and who have undergone re-vascularization with stent implantation to the infarct related artery (IRA). The anticipated recruitment target is 100 patients over a two-year period.
• Consenting participants who qualify during the screening process, will undergo apheresis. Randomization, through a web-based system will take place immediately after successful apheresis. The cell collection samples will be sent to a cell manufacturing facility for manufacturing according to the treatment allocation of: a)Placebo (Plasma-Lyte A & 25% autologous plasma), b)EPCs or c)EPCs transfected with human endothelial nitric oxide synthase (eNOS).
• Approximately 5-7 days later, the patient will receive the randomized treatment allocation via intracoronary injection into the IRA. Participants will remain in hospital overnight for continuous cardiac monitoring. The first post-delivery visit will take place the following morning before hospital discharge. Subsequent study visits will be clinic visits at 1 week, 1, 3 and 6 months after study treatment. Subsequently, a registry to collect long-term safety information from telephone contacts will continue annually for 10 years. During the registry period, participants will be allowed to volunteer for enrolment in other clinical trials.