Condition category
Circulatory System
Date applied
12/02/2010
Date assigned
17/02/2010
Last edited
19/09/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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@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 measures

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

01/12/2013

Reason abandoned

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

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

01/12/2013

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

http://www.ohri.ca

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes