Effects of Intracoronary Progenitor Cell Therapy on Coronary Flow Reserve After Acute MI

Study Overview
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Brief Summary
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Coronary flow reserve is an important measure of the integrity of the coronary microcirculation. Moreover, impaired coronary flow reserve is a predictor of future cardiovascular events and poor prognosis in patients after acute myocardial infarction. After acute myocardial infarction, coronary flow reserve remains significantly reduced. A previous randomized, double-blind Placebo-controlled trial (REPAIR-AMI) demonstrated complete normalization of coronary flow reserve after intracoronary application of autologous bone marrow-derived progenitor cells (but no effect in the placebo group) in patients with ST segment elevation myocardial infarction. The current study is planned to extend these findings to patients with Non-ST segment elevation myocardial infarction, since these patients have an equally reduced outcome.

Detailed Description
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Improvement of neovascularization is a key mechanism of functional improvement of intracoronary application of progenitor cells after acute myocardial infarction. Since capillary density cannot be assessed histological in patients, measurement of coronary flow reserve is an exact means for estimating capillary density and assessing coronary microvascular function. With the help of an intracoronary Doppler Wire, coronary hemodynamics can be assessed at baseline and, for example, adenosin-induced maximal vasodilation. Calculation of the minimal vascular resistance indices allows to estimate the cross-sectional area, reflecting capillary density, and, in comparison with the time of the acute myocardial infarction, estimation of improved neovascularization at a later timepoint. In order to improve neovascularization, which may then be associated with improved left ventricular contractility, we initiated the current trial.

Official Title
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Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Coronary Syndrome: REPAIR - ACS

Conditions
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Coronary Artery Disease, Acute Myocardial Infarction

Intervention / Treatment
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* Biological: autologous bone marrow-derived progenitor cells
* Biological: placebo medium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute coronary syndrome (ST-depression in at least 2 leads > 0,1 mV), or T-wave inversion, with or without elevated myocardial biomarkers (Troponin T oder I), together with typical clinical presentation), treated as follows: Acute percutaneous revascularization with stent implantation within 48 hours after symptom onset. Successful acute PCI (residual stenosis < 30%, TIMI flow > 2). Hemodynamic stability Age 18 - 80 years Written informed consent Active contraception in women of childbearing age Exclusion Criteria: Patients with STEMI (ST elevation in 2 leads above 0,2 mV in lead V1, V2 oder V3 or above 0,1 mV in the other leads) Necessity of additional PCI in non-infarct vessel at the time of study therapy (multi-vessel PCI in the acute event is possible) Heart failure (LVEF ≤ 30 %). Arteriovenous malformation or aneurysms Active infection (C-reactive protein > 10 mg/dl), or fever, or diarrhoea within the last 4 weeks Chronic inflammatory disease HIV infection or active hepatitis Neoplastic disease without documented complete remission within the last 5 years Recent stroke within the last 3 months Impaired kidney function (creatinin > 2,5 mg/dl) at the time of treatment Significant liver disease (GOT > 2x upper normal value or spontaneous INR > 1,5. Hematopoetic disease (anaemia with Hb< 8.5 mg/dl; thrombocytopenia < 100.000/µl; splenomegaly Known allergies to Clopidogrel, Heparin or Abciximab History of bleeding disorder GI bleeding within the last 3 months Major surgery or trauma within the last 2 months Uncontrolled hypertension Pregnancy Mental disability Previous progenitor cell therapy Participation in a different 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 |
| --- | --- |
| Active Comparator: 1<br>Intracoronary infusion of autologous bone marrow-derived progenitor cells after NSTEMI | Biological: autologous bone marrow-derived progenitor cells<br>* intracoronary infusion of autologous bone marrow-derived progenitor cells isolated from 50 ml bone marrow aspirate<br>|
| Placebo Comparator: 2<br>Intracoronary infusion of Placebo after NSTEMI | Biological: placebo medium<br>* intracoronary infusion of placebo medium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of coronary flow reserve in the infarct vessel |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of relative coronary flow reserve |  | 4 months | 
| Improvement of global and regional left ventricular ejection fraction |  | 4 months | 
| Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization) |  | 4 months | 
| Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization) |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intracoronary progenitor cell therapy, NSTEMI, coronary flow reserve, randomized doubleblind Placebo-controlled trial