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

Primary Purpose

Coronary Artery Disease, Acute Myocardial Infarction

Status

Terminated

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

autologous bone marrow-derived progenitor cells

placebo medium

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring intracoronary progenitor cell therapy, NSTEMI, coronary flow reserve, randomized doubleblind Placebo-controlled trial

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Med. Klinik III; Kardiologie
Universität Leipzig / Herzzentrum

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

Intracoronary infusion of autologous bone marrow-derived progenitor cells after NSTEMI

Intracoronary infusion of Placebo after NSTEMI

Outcomes

Primary Outcome Measures

Improvement of coronary flow reserve in the infarct vessel

Secondary Outcome Measures

Improvement of relative coronary flow reserve

Improvement of global and regional left ventricular ejection fraction

Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization)

Full Information

NCT ID

NCT00711542

First Posted

July 8, 2008

Last Updated

January 11, 2017

Sponsor

Johann Wolfgang Goethe University Hospital

Collaborators

University of Leipzig

1. Study Identification

Unique Protocol Identification Number

NCT00711542

Brief Title

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

Acronym

REPAIR-ACS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Terminated

Why Stopped

Slow recruitment

Study Start Date

September 2008 (undefined)

Primary Completion Date

December 2014 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Johann Wolfgang Goethe University Hospital

Collaborators

University of Leipzig

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronary Artery Disease, Acute Myocardial Infarction

Keywords

intracoronary progenitor cell therapy, NSTEMI, coronary flow reserve, randomized doubleblind Placebo-controlled trial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

31 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Intracoronary infusion of autologous bone marrow-derived progenitor cells after NSTEMI

Arm Title

Arm Type

Placebo Comparator

Arm Description

Intracoronary infusion of Placebo after NSTEMI

Intervention Type

Biological

Intervention Name(s)

autologous bone marrow-derived progenitor cells

Intervention Description

intracoronary infusion of autologous bone marrow-derived progenitor cells isolated from 50 ml bone marrow aspirate

Intervention Type

Biological

Intervention Name(s)

placebo medium

Intervention Description

intracoronary infusion of placebo medium

Primary Outcome Measure Information:

Title

Improvement of coronary flow reserve in the infarct vessel

Time Frame

4 months

Secondary Outcome Measure Information:

Title

Improvement of relative coronary flow reserve

Time Frame

4 months

Title

Improvement of global and regional left ventricular ejection fraction

Time Frame

4 months

Title

Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization)

Time Frame

4 months

Title

Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization)

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andreas M Zeiher, MD

Organizational Affiliation

Goethe University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Med. Klinik III; Kardiologie

City

Frankfurt

ZIP/Postal Code

60590

Country

Germany

Facility Name

Universität Leipzig / Herzzentrum

City

Leipzig

ZIP/Postal Code

04289

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

17620510

Citation

Erbs S, Linke A, Schachinger V, Assmus B, Thiele H, Diederich KW, Hoffmann C, Dimmeler S, Tonn T, Hambrecht R, Zeiher AM, Schuler G. Restoration of microvascular function in the infarct-related artery by intracoronary transplantation of bone marrow progenitor cells in patients with acute myocardial infarction: the Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial. Circulation. 2007 Jul 24;116(4):366-74. doi: 10.1161/CIRCULATIONAHA.106.671545. Epub 2007 Jul 9.

Results Reference

background

PubMed Identifier

17098754

Citation

Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Werner N, Haase J, Neuzner J, Germing A, Mark B, Assmus B, Tonn T, Dimmeler S, Zeiher AM; REPAIR-AMI Investigators. Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J. 2006 Dec;27(23):2775-83. doi: 10.1093/eurheartj/ehl388. Epub 2006 Nov 10.

Results Reference

background

PubMed Identifier

16990384

Citation

Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM; REPAIR-AMI Investigators. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1210-21. doi: 10.1056/NEJMoa060186.

Results Reference

background

PubMed Identifier

17951319

Citation

Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):208-16. doi: 10.1161/ATVBAHA.107.155317. Epub 2007 Oct 19.

Results Reference

background

PubMed Identifier

16598441

Citation

Schachinger V, Assmus B, Honold J, Lehmann R, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. Normalization of coronary blood flow in the infarct-related artery after intracoronary progenitor cell therapy: intracoronary Doppler substudy of the TOPCARE-AMI trial. Clin Res Cardiol. 2006 Jan;95(1):13-22. doi: 10.1007/s00392-006-0314-x.

Results Reference

background

PubMed Identifier

15489105

Citation

Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol. 2004 Oct 19;44(8):1690-9. doi: 10.1016/j.jacc.2004.08.014.

Results Reference

background

PubMed Identifier

12473544

Citation

Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002 Dec 10;106(24):3009-17. doi: 10.1161/01.cir.0000043246.74879.cd.

Results Reference

background

Links:

URL

http://www.kardiologie-uni-frankfurt.de/

Description

homepage cardiology university frankfurt

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

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