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

Phase 1

Terminated

• Conditions: Coronary Artery Disease; Acute Myocardial Infarction
• Interventions: Biological: placebo medium; Biological: autologous bone marrow-derived progenitor cells

• Registration Number: NCT00711542
• Lead Sponsor: Johann Wolfgang Goethe University Hospital

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.

Study Timeline

• Study First Submitted: 2008-07-08
• Study First Submitted QC: 2008-07-08
• Study First Posted: 2008-07-09
• Study Start: 2008-09
• Primary Completion: 2014-12
• Study Completion: 2015-12
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-11
• Last Update Posted: 2017-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 31

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	placebo medium	Intracoronary infusion of Placebo after NSTEMI
1	autologous bone marrow-derived progenitor cells	Intracoronary infusion of autologous bone marrow-derived progenitor cells after NSTEMI

Primary Outcome Measures

Name	Time	Method
Improvement of coronary flow reserve in the infarct vessel	4 months

Secondary Outcome Measures

Name	Time	Method
Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization)	12 months
Improvement of relative coronary flow reserve	4 months
Improvement of global and regional left ventricular ejection fraction	4 months

Trial Locations

Locations (2)

Med. Klinik III; Kardiologie; 🇩🇪 Frankfurt, Germany

Universität Leipzig / Herzzentrum; 🇩🇪 Leipzig, Germany