Effects of Intracoronary Progenitor Cell Therapy on Coronary Flow Reserve After Acute MI (REPAIR-ACS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Johann Wolfgang Goethe University Hospitals
Sponsor:
Collaborator:
University of Leipzig
Information provided by (Responsible Party):
A. M. Zeiher, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT00711542
First received: July 8, 2008
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Acute Myocardial Infarction
Biological: autologous bone marrow-derived progenitor cells
Biological: placebo medium
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Coronary Syndrome: REPAIR - ACS

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • Improvement of coronary flow reserve in the infarct vessel [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvement of relative coronary flow reserve [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Improvement of global and regional left ventricular ejection fraction [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization) [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
  • Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: September 2008
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Intracoronary infusion of autologous bone marrow-derived progenitor cells after NSTEMI
Biological: autologous bone marrow-derived progenitor cells
intracoronary infusion of autologous bone marrow-derived progenitor cells isolated from 50 ml bone marrow aspirate
Placebo Comparator: 2
Intracoronary infusion of Placebo after NSTEMI
Biological: placebo medium
intracoronary infusion of placebo medium

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00711542

Contacts
Contact: Andreas M Zeiher, MD +49 69 6301 ext 5789 zeiher@em.uni-frankfurt.de
Contact: Birgit Assmus, MD +49 69 6301 ext 7387 b.assmus@em.uni-frankfurt.de

Locations
Germany
Med. Klinik III; Kardiologie Recruiting
Frankfurt, Germany, 60590
Contact: Birgit Assmus, MD    +49 69 6301 ext 7387    b.assmus@em.uni-frankfurt.de   
Contact: Stefan Fichtlscherer, MD    +49 69 6301 ext 7387    fichtlscherer@em.uni-frankfurt.de   
Sub-Investigator: Birgit Assmus, MD         
Principal Investigator: Andreas M Zeiher, MD         
Universität Leipzig / Herzzentrum Recruiting
Leipzig, Germany, 04289
Contact: Gerhard Schuler, MD    +49 341 865 ext 1428    gerhard.schuler@medizin.uni-leipzig.de   
Contact: Sandra Erbs    +49 341 865 ext 1428    Sandra.Erbs@medizin.uni-leipzig.de   
Principal Investigator: Gerhard Schuler, MD         
Sub-Investigator: Sandra Erbs, MD         
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospitals
University of Leipzig
Investigators
Principal Investigator: Andreas M Zeiher, MD Goethe University
  More Information

Additional Information:
Publications:

Responsible Party: A. M. Zeiher, Prof. Dr. Andreas M. Zeiher, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier: NCT00711542     History of Changes
Other Study ID Numbers: 2007-08-16 REPAIR-ACS
Study First Received: July 8, 2008
Last Updated: November 14, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Johann Wolfgang Goethe University Hospitals:
intracoronary progenitor cell therapy
NSTEMI
coronary flow reserve
randomized doubleblind Placebo-controlled trial

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Infarction
Myocardial Infarction
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Ischemia
Necrosis
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on October 21, 2014