Myocardial Infarction
Conditions
Keywords
Acute myocardial infarction
Brief summary
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
* 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.
Interventions
BIOLOGICALIntracoronary infusion of enriched bone marrow-derived progenitor cells
BIOLOGICALPlacebo medium supplemented with autologous serum
Sponsors
Johann Wolfgang Goethe University Hospital
Blutspendedienst Baden-Württemberg - Hessen
Guidant Corporation
Eli Lilly and Company
A. M. Zeiher
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in global left ventricular function in quantitative LV angiography after 4 months. | baseline to 4 months | absolute delta LVEF (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Primary endpoint in patients without restenosis. | baseline to 4 months | absolute delta LVEF (%) |
| 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 | — |
| Amendment for extended follow up after 2 and 5 years: | 24 and 60 months | — |
Countries
Germany, Switzerland
Outcome results
None listed