Acute Myocardial Infarction
Conditions
Keywords
Acute Myocardial Infarction, Celltherapy, Bone Marrow
Brief summary
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).
Interventions
OTHERCD133+ infusion
Subjects will be infused with all available autologous CD133+ cells after processing during one infusion session (during angiography).
OTHERplacebo infusion
Buffered normal saline will be infused in the coronary artery during an angiography.
Sponsors
King's College London
Jozef Bartunek
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Belgium, France, Netherlands, United Kingdom
Outcome results
None listed