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

Coronary Artery Disease Clinical Trial

— REPAIR-ACS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00711542
• Other study ID #: 2007-08-16 REPAIR-ACS
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: July 8, 2008
• Last updated: January 11, 2017
• Start date: September 2008
• Est. completion date: December 2015

Study information

• Verified date: January 2017
• Source: Johann Wolfgang Goethe University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: December 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Coronary Artery Disease
• Coronary Disease
• Infarction
• Myocardial Infarction
• Myocardial Ischemia

Intervention

Biological:
• autologous bone marrow-derived progenitor cells
intracoronary infusion of autologous bone marrow-derived progenitor cells isolated from 50 ml bone marrow aspirate
• placebo medium
intracoronary infusion of placebo medium

Locations

Country	Name	City	State
Germany	Med. Klinik III; Kardiologie	Frankfurt
Germany	Universität Leipzig / Herzzentrum	Leipzig

Sponsors (2)

Lead Sponsor	Collaborator
Johann Wolfgang Goethe University Hospital	University of Leipzig

Country where clinical trial is conducted

Germany, 

References & Publications (7)

Assmus B, Schächinger V, Teupe C, Britten M, Lehmann R, Döbert N, Grünwald 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. — View Citation

Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):208-16. Review. — View Citation

Erbs S, Linke A, Schächinger 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. — View Citation

Schächinger 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. — View Citation

Schächinger 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. — View Citation

Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Süselbeck 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. — View Citation

Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Süselbeck 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of coronary flow reserve in the infarct vessel		4 months	No
Secondary	Improvement of relative coronary flow reserve		4 months	No
Secondary	Improvement of global and regional left ventricular ejection fraction		4 months	No
Secondary	Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization)		4 months	Yes
Secondary	Major adverse cardiac events (death, MI, rehospitalization for heart failure, revascularization)		12 months	Yes

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