The Enhanced Angiogenic Cell Therapy - Acute Myocardial Infarction Trial (ENACT-AMI)
Primary Purpose
Anterior Wall Myocardial Infarction
Status
Active
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Plasma-Lyte A and 25% Autologous Plasma
Autologous EPCs
Autologous EPCs Transfected with human eNOS
Sponsored by
About this trial
This is an interventional treatment trial for Anterior Wall Myocardial Infarction focused on measuring Stent, endothelial progenitor cells, nitric oxide, myocardial infarction, MRI
Eligibility 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
Sites / Locations
- University of Ottawa Heart Institute
- St. Michael's Hospital
- L'institut de cardiologie de Montreal
- Institut Universitaire de Cardiologie et de Pneumonologie de Québec - Université Laval
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Plasma-Lyte A and 25% autologous plasma
Autologous EPCs
Autologous EPCs Transfected with human eNOS
Arm Description
Outcomes
Primary Outcome Measures
Assessment of Global LVEF
A change in global left ventricular ejection fraction by cardiac MRI between those treated with cell/gene enriched EPCs versus placebo
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
Assessment of: Cardiac wall motion and volumes
Change in regional wall motion and regional wall thickening by cardiac MRI between the above patient groups
Change in echocardiographic assessment of LVEF, infarct size and ventricular volumes between the above patient groups
Time To Clinical Worsening (TTCW)
Quality of Life Measures: Participants will complete SF-36 and DASI questionnaires at baseline, 3 and 6 months.
Safety Measurements
Clinically significant changes in CK and troponin more than 24 hours post delivery
Clinically significant changes in ECG
Assessment of major acute cardiac events
Evidence of any systemic embolization during the hospitalization period
Need for revacularization procedures
Full Information
NCT ID
NCT00936819
First Posted
July 7, 2009
Last Updated
December 1, 2020
Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Institutes of Health Research (CIHR), Stem Cell Network
1. Study Identification
Unique Protocol Identification Number
NCT00936819
Brief Title
The Enhanced Angiogenic Cell Therapy - Acute Myocardial Infarction Trial
Acronym
ENACT-AMI
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 Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 19, 2013 (Actual)
Primary Completion Date
March 5, 2020 (Actual)
Study Completion Date
September 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Institutes of Health Research (CIHR), Stem Cell Network
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anterior Wall Myocardial Infarction
Keywords
Stent, endothelial progenitor cells, nitric oxide, myocardial infarction, MRI
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Plasma-Lyte A and 25% autologous plasma
Arm Type
Placebo Comparator
Arm Title
Autologous EPCs
Arm Type
Experimental
Arm Title
Autologous EPCs Transfected with human eNOS
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Plasma-Lyte A and 25% Autologous Plasma
Intervention Description
Single dose of 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Intervention Type
Biological
Intervention Name(s)
Autologous EPCs
Other Intervention Name(s)
Non-applicable
Intervention Description
Single dose of 20 million cells in 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Intervention Type
Biological
Intervention Name(s)
Autologous EPCs Transfected with human eNOS
Other Intervention Name(s)
Non-applicable
Intervention Description
Single dose of 20 million cells in 8 mls given by investigator via intracoronary injection into stent of infarct-related artery
Primary Outcome Measure Information:
Title
Assessment of Global LVEF
Description
A change in global left ventricular ejection fraction by cardiac MRI between those treated with cell/gene enriched EPCs versus placebo
Change in global left ventricular ejection fraction by cardiac MRI between those treated with non-transfected autologous EPCs versus eNOS transfected EPCs.
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Assessment of: Cardiac wall motion and volumes
Description
Change in regional wall motion and regional wall thickening by cardiac MRI between the above patient groups
Change in echocardiographic assessment of LVEF, infarct size and ventricular volumes between the above patient groups
Time Frame
Baseline to 6 months
Title
Time To Clinical Worsening (TTCW)
Description
Quality of Life Measures: Participants will complete SF-36 and DASI questionnaires at baseline, 3 and 6 months.
Time Frame
Baseline to 6 months
Title
Safety Measurements
Description
Clinically significant changes in CK and troponin more than 24 hours post delivery
Clinically significant changes in ECG
Assessment of major acute cardiac events
Evidence of any systemic embolization during the hospitalization period
Need for revacularization procedures
Time Frame
Baseline to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Duncan Stewart, MD, FRCP C
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
L'institut de cardiologie de Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 1C8
Country
Canada
Facility Name
Institut Universitaire de Cardiologie et de Pneumonologie de Québec - Université Laval
City
Québec
ZIP/Postal Code
G1V 4G5
Country
Canada
12. IPD Sharing Statement
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The Enhanced Angiogenic Cell Therapy - Acute Myocardial Infarction Trial
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