Contact information
Type
Scientific
Primary contact
Dr Duncan J Stewart
ORCID ID
Contact details
Ottawa Hospital General Campus
Sprott Centre for Stem Cell Research
501 Smyth Road
Critical Care Wing - 5th Floor
Room 5206 - Box 511
Ottawa
K1H 8L6
Canada
+1 613 737 8899 ext. 79017
djstewart@toh.ca
Type
Scientific
Additional contact
Ms Rose Gauset
ORCID ID
Contact details
Regenerative Medicine Clinical Research
Ottawa Hospital Research Institute (OHRI)
10 Harvard Court
Riverview
New Brunswick
Riverview
E1B 4S3
Canada
-
rgaudet@ohri.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00936819
Protocol/serial number
MCT-90169
Study information
Scientific title
Enhanced Angiogenic Cell Therapy in Acute Myocardial Infarction: a multicentre, phase IIb randomised placebo-controlled trial
Acronym
ENACT-AMI
Study hypothesis
The primary objectives of this study are to determine whether endothelial-like culture modified mononuclear cell (E-CMM) therapy is effective in improving cardiac function following acute myocardial infarction, and whether 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 therapy (5 - 10 days versus 11 - 30 days).
Ethics approval
Not provided at time of registration
Study design
Phase IIb double-blind parallel randomised placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Acute myocardial infarction
Intervention
After providing informed consent, all participants who meet the eligibilty criteria will undergo apheresis. Apheresis is performed to obtain mononuclear cells from the participant's blood. These cells are sent to a site-specific cell manufacturing lab where they will be processed according to the random allocation. The random allocation will be to:
1. Endothelial-like circulating mononuclear cells (E-CMMs)
2. E-CMMs transfected with human eNOS
3. Plasma-lyte A
Approximately 5 days later, the participant will receive the study treatment via intracoronary injection through the distal stent of the IRA during coronary angiography in the catheterisation suite. Study follow-up will include clinic visits the day after cell therapy, at 6 weeks, 3 and 6 months post-injection.
Secondary sponsor details:
Canadian Stem Cell Network (Canada)
501 Smyth Road, Room CCW-6189
Ottawa, Ontario K1H 8L6
Canada
Tel: +1 613 739 6675
Email: info@stemcellnetwork.ca
Intervention type
Other
Phase
Phase II/III
Drug names
Primary outcome measure
To measure the change in global left ventricular ejection fraction (LVEF) from baseline to 6 months after study treatment as determined by magnetic resonance imaging (MRI).
Secondary outcome measures
Measure changes from baseline to 6 months after study treatment of:
1. Regional wall motion, wall thickening and infarct volume as determined by cardiac MRI
2. Echocardiographic assessment of LVEF and ventricular volumes
3. Time to clinical worsening (death, hospitalisation for angina, reinfarction)
4. Quality of life (36-item short form health survey [SF-36] and Duke Activity Status Index [DASI] questionnaires)
Overall trial start date
01/05/2010
Overall trial end date
18/09/2029
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or female between 18 - 75 years of age
2. Clinical diagnosis of ST-elevation myocardial infarction (MI) of greater than 1 mm in two adjacent electrocardiogram (ECG) limb leads, or greater than 2 mm in two adjacent ECG precordial leads, or a new left bundle branch block and an increase in cardiospecific enzymes (creatine kinase [CK] greater than 3 x upper limit of normal [ULN]), and either positive myocardial bands (MB) fraction or increase in troponin compared to institutional laboratory normal ranges
3. Patients who have suffered an acute Q-wave MI within the preceding 30 days prior to inclusion and have undergone percutaneous coronary intervention (PCI) with stent implantation in the infarct related artery (IRA)
4. Culprit artery must have distal flow greater than thrombolysis in myocardial infarction (TIMI) 1
5. Left ventricular ejection fraction (LVEF) less than or equal to 45% by echocardiography (Simpson's Method) performed at least 2 days after onset of chest pain
6. In the case of previous MI, must have documentation of LVEF greater than 45% prior to index AMI
7. Females who are surgically sterile, or are post-menopausal, or have documented infertility, or are of child-bearing potential using one of the following methods of contraception:
7.1. Barrier-type devices (e.g., condom, diaphragm) used in combination with a spermicide; a double barrier method is recommended
7.2. Intrauterine devices (IUDs)
7.3. Oral or implanted contraceptives, if used in combination with a barrier method
8. Provided written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Total final enrolment
47
Participant exclusion criteria
1. Significant unprotected left main disease (greater than 50% stenosis) on diagnostic angiography
2. Planned coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) for a coronary stenosis greater than 70% in the non-infarct related artery (IRA)
3. History of sustained ventricular arrhythmias not related to AMI (evidenced by previous holter monitoring +/- medication history for sustained ventricular arrhythmias in the subject's medical chart
4. History of cerebrovascular accident or transient ischaemic attack less than or equal to 6 months
5. Any exclusion to magnetic resonance imaging (MRI) (includes already implanted automatic internal defibrillator or permanent pacemaker). Recent stent implantation is NOT an exclusion to MRI.
6. Persistent haemodynamic instability (need for ongoing pharmacological or mechanical support greater than 24 hours of the onset of chest pain)
7. Mechanical ventilatory support
8. Significant cardiac valvular disease
9. Left ventricular (LV) dysfunction from any other cause (e.g., non-ischaemic cardiomyopathy, collagen diseases)
10. Clinical evidence of persistent heart failure not responding to standard oral therapy
11. Clinical evidence of persistent ischaemia at time of cell therapy
12. Current pregnancy or nursing mothers
13. Known history of human immunodeficiency virus (HIV)
14. Known history of hepatitis B or C (hepatitis B surface antigen [HBsAg], hepatitis B [HB] core, hepatitis C [HC] antibody)
15. History of untreated ethanol (ETOH) or drug abuse
16. Creatinine clearance less than 60 by Cockcroft-Gault calculator (SI units)
17. Contraindications to apheresis (inadequate venous access or haematological exclusions)
18. Evidence of active infection
19. Significant co-morbidity (e.g., immunocompromise, hepatic failure)
20. Known history of malignancy in the past 5 years (except for low-grade and fully resolved non-melanoma skin cancer)
21. Known allergy to gentamycin and amphotericin
22. Patients receiving other investigational drug or device therapy within 30 days of screening
23. Patients who have received gene therapy
24. Inability ot provide informed consent and comply with the follow-up visit schedule
Recruitment start date
01/05/2010
Recruitment end date
15/09/2019
Locations
Countries of recruitment
Canada
Trial participating centre
Ottawa Hospital General Campus
Ottawa
K1H 8L6
Canada
Sponsor information
Organisation
Ottawa Hospital Research Institute (OHRI) (Canada)
Sponsor details
Ottawa Hospital General Campus
Sprott Centre for Stem Cell Research
501 Smyth Road
Critical Care Wing - 5th floor
Room 5206 - Box 511
Ottawa
K1H 8L6
Canada
+1 613 737 8899 ext. 79017
djstewart@ohri.ca
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-90169)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2010 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/20211295 (added 11/04/2019)