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

• ClinicalTrials.gov Identifier: NCT00936819
• Recruitment Status: Recruiting
• First Posted: July 10, 2009
• Last Update Posted: February 7, 2018
• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Canadian Institutes of Health Research (CIHR); Stem Cell Network
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

Study Description

Brief Summary:

This will be the first clinical trial to include a strategy designed to enhance the function of autologous progenitor cells by overexpressing eNOS, and the first to use combination gene and cell therapy for the treatment of cardiac disease.

Condition or disease	Intervention/treatment	Phase
Anterior Wall Myocardial Infarction	Biological: Plasma-Lyte A and 25% Autologous Plasma; Biological: Autologous EPCs; Biological: Autologous EPCs Transfected with human eNOS	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase IIb, Randomized, Double-blind, Placebo Controlled Study Using Transplantation of Autologous Early Endothelial Progenitor Cells(EPCs) for Patients Who Have Suffered Acute Myocardial Infarction
• Study Start Date: July 2013
• Estimated Primary Completion Date: December 2018
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Plasma-Lyte A and 25% autologous plasma	Biological: Plasma-Lyte A and 25% Autologous Plasma; Single dose of 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Experimental: Autologous EPCs	Biological: Autologous EPCs; Single dose of 20 million cells in 8 mls given by investigator via intracoronary injection into stent of infarct-related artery; Other Name: Non-applicable
Experimental: Autologous EPCs Transfected with human eNOS	Biological: Autologous EPCs Transfected with human eNOS; Single dose of 20 million cells in 8 mls given by investigator via intracoronary injection into stent of infarct-related artery; Other Name: Non-applicable

Outcome Measures

Primary Outcome Measures :

1. Assessment of Global LVEF [ Time Frame: Baseline to 6 months ]
   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.

Secondary Outcome Measures :

1. Assessment of: Cardiac wall motion and volumes [ Time Frame: Baseline to 6 months ]
   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
2. Time To Clinical Worsening (TTCW) [ Time Frame: Baseline to 6 months ]
   Quality of Life Measures: Participants will complete SF-36 and DASI questionnaires at baseline, 3 and 6 months.
3. Safety Measurements [ Time Frame: Baseline to 6 months ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female 18-80 years of age
• Clinical diagnosis of anterior ST-elevation myocardial infarction within the last 30 days, with any one of the following 12-lead electrocardiographic changes:
• a) Greater than or equal to 1 mm ST elevation or new Q waves in 2 adjacent electrocardiographic precordial leads
• b) A new left bundle branch block AND and for patients presenting within 3 days of onset of chest pain an increase in cardiospecific enzymes (>3x CK with, EITHER positive MB fraction or increase in troponin compared to institution laboratory normal ranges)
• Successful PCI with stent implantation to infarct-related artery within the last 30 days; defined as residual stenosis no greater than 30%, TIMI flow of at least 2 or greater and a reference diameter of at least > 2mm
• Is considered hemodynamically stable at time of enrollment and immediately prior to cell delivery
• Screening LVEF must be no greater than 45% by echocardiography (determined by Simpson's method) performed at least 4 days after revascularization procedure. (All screening echos done within the first 4 days post-PCI must be repeated either by echocardiography or MRI prior to cell delivery to ensure that the variability does not exceed 10%)
• In the case of a previous myocardial infarction, documented LVEF must be 55% or greater
• Female participants MUST be surgically sterile, post-menopausal, have documented infertility, or are of child-bearing potential wih laboratory confirmation of non-pregnant state
• Provided written informed consent and is willing to comply with study follow-up visits

Exclusion Criteria:

• Significant unprotected left main disease (stenosis of 50% or greater on diagnostic angiography)
• An increase in LVEF by greater that 10% from initial LVEF evaluation for repeat assessments
• The presence of significant coronary lesions, other than the index lesion of the IRA
• A history of significant ventricular arrhythmia NOT related to index STEMI
• A history of cerebro-vascular accident or transient ischemic attack within 6 months of enrollment
• Meets at least one exclusion criterion for MRI (NB: Recent stent implantation is not an exclusion)
• Inability to undergo apheresis procedure (i.e.: poor venous access, laboratory abnormalities)
• A history of uncorrected significant valvular heart disease
• A history of left ventricular dysfunction prior to index STEMI
• A history of human immunodeficiency virus (HIV) or hepatitis B or C infection
• A history of malignancy within 5 years (Except for low-grade and fully resolved non-melanoma skin cancer)
• A history of allergy to gentamycin or amphotericin
• A history of Heparin-Induced Thrombocytopenia (HIT)
• A history of non-compliance
• Active inflammatory autoimmune disease requiring chronic immunosuppressive therapy
• Creatinine clearance <60 by Cockcroft-Gault Calculator
• Confirmed pregnant or lactating
• Is enrolled in a current investigational drug or device trial
• Participant has received cell or gene therapy in past
• The presence of any significant co-morbidities that, in the investigator's opinion, would preclude the participant from taking part in the trial
• Inability to provide informed consent and comply with the follow-up visit schedule

Contacts and Locations

Contacts

Contact: Dr. Duncan J. Stewart, MD FRCP C; (613) 737-8899 ext 79017; djstewart@ohri.ca

Contact: Rose Gaudet, BA; (613) 798-5555 ext 13633; rgaudet@ohri.ca

Locations

Canada, Ontario

University of Ottawa Heart Institute; Recruiting

Ottawa, Ontario, Canada, K1Y 4W7

Contact: Christopher Glover, MD FRCP C (613) 696-7329 cglover@ottawaheart.ca

Contact: Christina Osborne (613) 696-7000 ext 13105 cosborne@ottawaheart.ca

Principal Investigator: Christopher Glover, MD FRCP C

Sub-Investigator: Alexander Dick, MDCRP C

Sub-Investigator: Le May Michel, MD

St. Michael's Hospital; Recruiting

Toronto, Ontario, Canada, M5B 1W8

Contact: Michael Kutryk, MDFRCP C 416-864-6060 ext 6155 kutrykm@smh.toronto.on.ca

Contact: Maria (Krisel) Abulencia, RN 416-864-6060 ext 4130 abulenciama@smh.ca

Principal Investigator: Michael Kutryk, MD

Canada, Quebec

L'institut de cardiologie de Montreal; Recruiting

Montreal, Quebec, Canada, H1T 1C8

Contact: Quoc Hung.Ly, MD FRCP C 514-376-3330 ext 2438 hung.ly@icm.mhi.org

Contact: Luc Harvey, RN 514-376-3330 ext 2776 luc.harvey@icm-mhi.org

Principal Investigator: Quoc Hung-Ly, MDFRCP C

Canada

Institut Universitaire de Cardiologie et de Pneumonologie de Québec - Université Laval; Recruiting

Québec, Canada, G1V 4G5

Contact: Josep Rodés-Cabau, MD 418-656-8711 ext 5593 Josep.Rodes@criucpq.ulaval.ca

Contact: Mélaine Henry 418-656-8711 ext 2702 melaine.henry@criucpq.ulaval.ca

Principal Investigator: Josep Rodés-Cabau, MD

Sub-Investigator: Vincent Laroche, MD

Sponsors and Collaborators

Ottawa Hospital Research Institute

Canadian Institutes of Health Research (CIHR)

Stem Cell Network

Investigators

• Principal Investigator: Duncan Stewart, MD, FRCP C; Ottawa Hospital Research Institute

More Information

• Responsible Party: Ottawa Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT00936819 History of Changes
• Other Study ID Numbers: 2008-872; ISRCTN47943321 ( Registry Identifier: controlled-trials.com )
• First Posted: July 10, 2009
• Last Update Posted: February 7, 2018
• Last Verified: February 2018

Keywords provided by Ottawa Hospital Research Institute:

Stent; endothelial progenitor cells; nitric oxide; myocardial infarction; MRI

Additional relevant MeSH terms:

Myocardial Infarction; Anterior Wall Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Plasma-lyte 148; Ophthalmic Solutions; Pharmaceutical Solutions