Acute Myocardial Infarction, Coronary Artery Disease
Conditions
Keywords
intracoronary progenitor cell therapy, NSTEMI, coronary flow reserve, randomized doubleblind Placebo-controlled trial
Brief summary
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
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.
Interventions
BIOLOGICALautologous bone marrow-derived progenitor cells
intracoronary infusion of autologous bone marrow-derived progenitor cells isolated from 50 ml bone marrow aspirate
BIOLOGICALplacebo medium
intracoronary infusion of placebo medium
Sponsors
University of Leipzig
Johann Wolfgang Goethe University Hospital
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Improvement of coronary flow reserve in the infarct vessel | 4 months |
Secondary
| Measure | 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 |
Countries
Germany
Outcome results
None listed