A Trial Using CD133 Enriched Bone Marrow Cells Following Primary Angioplasty for Acute Myocardial Infarction

Study Overview
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Brief Summary
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An international, multi-centre, double-blind, randomised, placebo-controlled clinical trial with central core lab analyses to determine the safety of intra-coronary infusion of enriched CD133+, bone marrow-derived, autologous progenitor cells in patients 5-10 days after acute percutaneous coronary revascularization (primary PCI) for ST-segment elevation myocardial infarction (STEMI).

Official Title
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A Multi-Centre, Double-Blind, Randomised, Placebo-Controlled Trial Using CD133 Enriched Bone Marrow Cells Following Primary Angioplasty for Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Other: CD133+ infusion
* Other: placebo infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary PCI for acute STEMI between 2-24 hours after onset of chest pain. ST-segment elevation >=2mm in >=3 adjacent leads. Presence of severe hypokinesia and/or akinesia in >=2 adjacent segments on echocardiogram at 48-72 hrs after primary PCI. Age between 20 and 75 years. Exclusion Criteria: Pregnant or lactating. Prior history of myocardial infarction before index event. Decompensated congestive heart failure. Pre-existent LV dysfunction (EF <45% prior to admission) Cardiomyopathy. Previous cardiac surgery. Congenital heart disorder. Serum creatinine >200 Mmol/L. Presence of permanent pacemaker or implantable defibrillator. Contraindication to bone marrow aspiration. History of malignancy within 5 years except curatively treated basal cell carcinoma, squamous cell carcinoma and/or cervical carcinoma. Sustained or inducible VT >48 hours post primary PCI. Three vessel coronary artery disease necessitating intervention within 4 months. Immune compromise including chronic human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Presence of chronic systemic inflammatory disorders. Previous autologous or allogeneic bone marrow or peripheral stem cell transplant or prior solid organ transplantation. Low hemoglobin, white blood cell, absolute neutrophil and/or platelet count. Any condition associated with a life expectancy of less than 6 months. Participation in unrelated research involving investigational pharmacological agent(s) 30 days before planned dosing. Current alcohol or drug abuse. Inability to provide written informed consent.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Enriched CD133+, bone marrow-derived, autologous progenitor cells for this trial will be infused in the coronary arteries | Other: CD133+ infusion<br>* Subjects will be infused with all available autologous CD133+ cells after processing during one infusion session (during angiography).<br>|
| Placebo Comparator: 2<br>Control group patients will receive 3 injections of 0.3 mL each of buffered normal saline (the vehicle used for cell suspension) into comparable vessels. Subjects will have an identical intra-coronary injection procedure to those randomized to autologous CD133+ progenitor cell injections. | Other: placebo infusion<br>* Buffered normal saline will be infused in the coronary artery during an angiography.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PRIMARY SAFETY ENDPOINT Comparison of progression in coronary atherosclerosis burden proximal and distal to the stented segment of the infarct-related artery in treated and control groups. |  | at 6 months post-infusion | 
| PRIMARY EFFICACY ENDPOINT Comparison of changes in myocardial thickening in non-viable akinetic / hypokinetic LV wall segments as determined by cardiac magnetic resonance imaging (cMRI) in treated and control groups. |  | at 6 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SECONDARY SAFETY ENDPOINT (a) Development of ventricular arrhythmias including failed sudden cardiac death. (b) Development of congestive heart failure. |  | At all follow up's | 
| SECONDARY EFFICACY ENDPOINTS (a) Changes in % global LV ejection fraction (EF) compared with baseline as determined by cMRI and echocardiography pre- and post-cell infusion subsequent to primary PCI. |  | at all follow up's | 
| SECONDARY EFFICACY ENDPOINTS (b)Assessment of epicardial resistance and microvascular resistance, index of myocardial resistance and absolute coronary blood flow measurements in the infarct related artery. |  | at 6 months follow up | 
| SECONDARY EFFICACY ENDPOINTS (c) The feasibility of the CliniMACS® Reagent System to yield 5x106 CD133+ cells from 100-150 ml of autologous bone marrow. |  | prior to the infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myocardial Infarction, Celltherapy, Bone Marrow