Meta-Analysis of Cell-based CaRdiac stUdiEs: ACCRUE

Study Overview
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Brief Summary
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Numerous human cardiac stem cell studies have been published, including relatively small number of patients. Meta-analysis of randomized trials have reported safety and a 3-6% increase in global left ventricular performance after intracoronary stem cell therapy in patients with acute myocardial infarction. Since most of the studies used different type of stem cells, delivery modes, and patient population, the results are heterogenous, therefore the comparison of the results is biased regarding generalizable conclusions about the effect of treatment. The present comparative meta-analysis is based on individual patient data, and gathers and pools the raw data, and analyzes the clinical outcome, safety and efficacy of the cardiac stem cell therapy.

Detailed Description
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Background: Many clinical trials and meta-analyses presented moderate but significant improvement of the left ventricular ejection fraction (LVEF) after intracoronary autologous bone-marrow (BM) or peripheral blood origin stem cells transfer. However, it remains controversial, whether this beneficial effects is comparable with the intramyocardial delivery of the stem cells, or could be maintained during moderate and long term follow-up. The BOOST trial suggested that cardiac stem cell therapy did not improve LVEF at 5-year follow-up. By contrast, BALANCE study showed a long sustained benefit of BM-stem cells treatment. Due to these divergent outcomes of the presented trials, the aim of the present meta-analysis is to compare the safety and effectiveness of the cardiac stem cell therapy in different patient population, delivery mode and cell type, to find out, which patients with which therapy mode can have the greatest benefit from cardiac stem cell therapy. Study design: individual patient data meta-analysis Data sources: European Centre performing human cardiac stem cell therapy have been contacted calling for participation. Methods: Individual data gathering and entering into the database for a pooled analysis. The meta-analysis will be done in line with recommendation from the Cochrane Collaboration and the Quality of Reporting of Meta-analyses guidelines with Review Manager 5.0. Fixed-effect model will be used.

Official Title
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Meta-Analysis of Cell-based CaRdiac stUdiEs: ACCRUE

Conditions
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Ischemic Heart Disease

Intervention / Treatment
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* Other: cell therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient included in one of the registered cell-based cardiac therapy of the participating center Exclusion Criteria: none

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Myocardial infarction<br>Patients with post-myocardial infarction receiving cell therapy either intracoronarily or intramyocardial | Other: cell therapy<br> <br> |
| Ischemic cardiomyopathy<br>Patients with ischemic cardiomyopathy treated with cell therapy either intracoronarily or intramyocardial | Other: cell therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from occurrence of major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, re-infarction, revascularization and stroke | MACCE is defined as all-cause death, re-infarction, revascularization and stroke | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hard clinical end point | all-cause death, re-infarction and stroke | 12 months | 
| Changes in end-diastolic volume | End-diastolic volume is an index of ventricular remodeling | 12 months | 
| Changes in end-systolic volume | Index of ventricular systolic performance | 12 months | 
| Changes in ejection fraction | Improvement of systolic cardiac function after cell therapy | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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meta-analysis, stem cell, cardiac, remodeling, ACCRUE