REPAIR-AMI: Intracoronary Progenitor Cells in Acute Myocardial Infarction (AMI)

Study Overview
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Brief Summary
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Impaired contractile function after a heart attack of the heart is a major cause of heart failure limiting quality of life and prognosis, which cannot be prevented even with optimal standard therapy, including immediate balloon/stent dilation of the infarct vessel. The aim of the REPAIR-AMI trial is to investigate whether infusion of progenitor cells into the infarct vessel (after successful reperfusion therapy) may improve left ventricular contractile function compared to placebo therapy. After bone marrow aspiration progenitor cells are enriched via a centrifugation method.

Detailed Description
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The study is a double-blind, placebo-controlled, randomized, multicenter trial. Patients after an acute myocardial infarction, undergoing successful reperfusion therapy are included. All patients undergo bone marrow aspiration 3 to 6 days after the infarction. After cell processing, enriched bone marrow-derived progenitor cells or placebo medium is infused direct into the infarct related artery during stop-flow. In addition, a left ventricular angiography is performed. After 4 months left ventricular angiography is repeated. The primary endpoint is the difference in change of left ventricular ejection fraction between the two groups.

Official Title
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Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Myocardial Infarction (REPAIR - AMI)

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Biological: Intracoronary infusion of enriched bone marrow-derived progenitor cells
* Biological: Placebo medium supplemented with autologous serum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute myocardial infarction (ST elevation in at least 2 leads >= 0.2 mV in V1,V2 or V3 or >= 0.1 mV in other leads), treated by one of the following procedures Either acute PCI with stent implantation within 24 hours after symptom onset or treatment with thrombolysis within 12 hours of symptom onset followed by PCI with stent implantation within 24 hours after thrombolysis. Acute PCI / stent implantation has been successful (residual stenosis visually < 30% and TIMI flow >= 2). At the time of inclusion patient does no longer require i.v. catecholamines or mechanical hemodynamic support (aortic balloon pump) Significant regional wall motion abnormality in LV angiogram at the time of acute PCI (ejection fraction <= 45% on visual estimation). Maximal CK elevation >= 400 U/l (measured at 37° C) with significant MB fraction > 6% Age 18 - 80 Years Written informed consent Exclusion Criteria: Regional wall motion abnormality outside the area involved in the index acute myocardial infarction. Need to revascularize additional vessels, outside the infarct artery. Arteriovenous malformations or aneurysms Active infection (CRP > 10 mg/dl) now, or fever or diarrhea within last 4 weeks. Chronic inflammatory disease HIV infection or active hepatitis Neoplastic disease without documented remission within the past 5 years. Cerebrovascular insult within 3 months Impaired renal function (creatinine > 2 mg/dl) at the time of cell therapy Significant liver disease (GOT > 2x upper limit) or spontaneous INR > 1,5) Anemia (hemoglobin < 8.5 mg/dl) Platelet count < 100.000/µl Hypersplenism Known allergy or intolerance to clopidogrel, heparin or abciximab. History of bleeding disorder Gastrointestinal bleeding within 3 months Major surgical procedure or traumata within 2 months Uncontrolled hypertension Pregnancy Mental retardation Previously performed stem / progenitor cell therapy Participation in another clinical trial within the last 30 days.

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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMC<br>Intracoronary infusion of autologous bone marrow derived cells | Biological: Intracoronary infusion of enriched bone marrow-derived progenitor cells<br> <br> |
| Placebo Comparator: Placebo<br>Intracoronary infusion of Placebo medium | Biological: Placebo medium supplemented with autologous serum<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in global left ventricular function in quantitative LV angiography after 4 months. | absolute delta LVEF (%) | baseline to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint in patients without restenosis. | absolute delta LVEF (%) | baseline to 4 months | 
| Improvement of regional wall motion in infarct area |  | baseline to 4 months | 
| Reduction of LV end-systolic volume |  | baseline to 4 months | 
| Major adverse cardiac events (MACE) |  | at 4, 12 and 60 months | 
| Rehospitalization due to heart failure. |  | 4, 12, 60 months | 
| NYHA status after 12 months |  | 12 months | 
| Amendment for extended follow up after 2 and 5 years: |  | 24 and 60 months | 
| outcomes in major adverse cardiac events (MACE) |  | 4, 12, 60 months | 
| Rehospitalization due to heart failure |  | 4, 12, 60 months | 
| NYHA status |  | 4, 12, 60 months | 
| patients in MRI subgroup: improvement in left ventricular function |  | 4, 12, 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myocardial infarction