Safety and Efficacy of Intracoronary Adult Human Mesenchymal Stem Cells After Acute Myocardial Infarction

Study Overview
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Brief Summary
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Early reperfusion strategies in tandem with remarkable advances in drugs and devices for treating myocardial infarction (MI) have contributed to a reduction in early mortality, but cardiovascular disease remains the leading cause of death worldwide. Current management strategies cannot solve the problem of cardiomyocyte loss and consequent progression of heart failure. In this respect, stem-cell therapy has shown potential benefits for repairing the damaged myocardium. Mesenchymal stem cells (MSCs) have been considered to be attractive therapeutic candidates because of their high capacity for replication: paracrine effect: ability to preserve potency: and because they do not cause adverse reactions to allogeneic versus autologous transplants. Intracoronary injection of stem cells seems to be safe, but only one clinical trial using MSCs via the intracoronary route in the setting of acute myocardial infarction (AMI) has been carried out. The investigators therefore assessed the safety and efficacy of intracoronary autologous bone marrow (BM)-derived human MSCs in patients with AMI.

Official Title
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A Randomized, Open-label, Multicenter Trial for the Safety and Efficacy of Intracoronary Adult Human Mesenchymal Stem Cells After Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Mesenchymal stem cell
* Drug: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-70 years ischemic chest pain for >30 min admitted to hospital <24 h after the onset of chest pain electrocardiography showed ST segment elevation >1 mm in two consecutive leads in the limb leads or >2 mm in the precordial leads they could be enrolled in the study <72 h after successful revascularization Exclusion Criteria: cardiogenic shock (defined as systolic blood pressure <90 mmHg requiring intravenous pressors or intra-aortic balloon counterpulsation) life-threatening arrhythmia impossible conditions for cardiac catheterization advanced renal or hepatic dysfunction history of previous coronary artery bypass graft history of hematologic disease history of malignancy major bleeding requiring blood transfusion stroke or transient ischemic attack in the previous 6 months structural abnormalities of the central nervous system (brain tumor, aneurysm, history of surgery) traumatic injury after myocardial infarction use of corticosteroids or antibiotics during the previous month major surgical procedure in the previous 3 months cardiopulmonary resuscitation for >10 min within the previous 2 weeks positive skin test for penicillin positive result for viral markers (human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Venereal Disease Research Laboratory (VDRL) test) pregnancy, possible candidate for pregnancy or breastfeeding females drug abusers inappropriate patients to participate in the study according to the chief investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mesenchymal stem cell treatment group<br> | Drug: Mesenchymal stem cell<br>* Route : intracoronary injection Frequency : single dose of autologous bone-marrow derived mesenchymal stem cells Dosage : 1x1000000 cells/kg Duration : mean injection duration approximately 4 weeks after primary percutaneous coronary intervention<br>* Other names: Hearticellgram-AMI;|
| Placebo Comparator: Control group<br>All patients were required to have successful revascularization of an infarct-related artery on coronary angiography at the time of randomization. All patients received aspirin (300 mg loading dose, then 100 mg daily) and clopidogrel (600 mg loading dose, then 75 mg daily) with optimal medical therapy according to the American College of Cardiology (ACC)/ American Heart Association (AHA) guidelines for treatment of ST-segment elevation myocardial infarction (STEMI) | Drug: Control group<br>* No additional treatment of mesenchymal stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute changes in global LVEF by SPECT | Absolute changes in global left ventricular ejection fraction (LVEF) as measured by SPECT 6 months after cell infusion | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in left ventricular end-diastolic volume (LVEDV) |  | baseline and 6 months | 
| Changes in left ventricular end-systolic volume (LVESV) |  | baseline and 6 months | 
| Changes in regional wall motion score index (WMSI) by Echocardiography |  | baseline and 6 months | 
| Major adverse cardiac event (MACE) | MACE was defined as the composites of any cause of death, myocardial infarction, revascularization of the target vessel, re-hospitalization for heart failure, and life-threatening arrhythmia. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cells, Myocardial infarction, Left ventricular dysfunction