REPAIR-AMI: Intracoronary Progenitor Cells in Acute Myocardial Infarction (AMI) - Full Text View

Sponsor:	Johann Wolfgang Goethe University Hospitals
Collaborators:	Blutspendedienst Baden-Württemberg - Hessen Guidant Corporation Eli Lilly and Company
Information provided by:	Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:	NCT00279175

Purpose

Impaired contractile function after a heart attack of the heart is a major cause of "heart failure" limiting quality of life and prognosis, which cannot be prevented even with optimal standard therapy, including immediate balloon/stent dilation of the infarct vessel.

The aim of the REPAIR-AMI trial is to investigate whether infusion of progenitor cells into the infarct vessel (after successful reperfusion therapy) may improve left ventricular contractile function compared to placebo therapy. After bone marrow aspiration progenitor cells are enriched via a centrifugation method.

Condition	Intervention	Phase
Myocardial Infarction	Biological: Intracoronary infusion of enriched bone marrow-derived progenitor cells Biological: Placebo medium supplemented with autologous serum	Phase 3

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 Myocardial Infarction (REPAIR - AMI)

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack Heart Failure

U.S. FDA Resources

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

Primary Outcome Measures:

Change in global left ventricular function in quantitative LV angiography after 4 months.

Secondary Outcome Measures:

Primary endpoint in patients without restenosis.
Improvement of regional wall motion in infarct area
Reduction of LV end-systolic volume
Major adverse cardiac events (MACE)
Rehospitalization due to heart failure.
NYHA status after 12 months
Amendment for extended follow up after 2 and 5 years:
outcomes in major adverse cardiac events (MACE)
Rehospitalization due to heart failure
NYHA status
patients in MRI subgroup: improvement in left ventricular function

Estimated Enrollment:	200
Study Start Date:	April 2004
Study Completion Date:	December 2010
Primary Completion Date:	October 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BMC Intracoronary infusion of autologous bone marrow derived cells	Biological: Intracoronary infusion of enriched bone marrow-derived progenitor cells
Placebo Comparator: Placebo Intracoronary infusion of Placebo medium	Biological: Placebo medium supplemented with autologous serum

Detailed Description:

The study is a double-blind, placebo-controlled, randomized, multicenter trial.
Patients after an acute myocardial infarction, undergoing successful reperfusion therapy are included.
All patients undergo bone marrow aspiration 3 to 6 days after the infarction.
After cell processing, enriched bone marrow-derived progenitor cells or placebo medium is infused direct into the infarct related artery during stop-flow. In addition, a left ventricular angiography is performed.
After 4 months left ventricular angiography is repeated. The primary endpoint is the difference in change of left ventricular ejection fraction between the two groups.

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 myocardial infarction (ST elevation in at least 2 leads >= 0.2 mV in V1,V2 or V3 or >= 0.1 mV in other leads), treated by one of the following procedures
- Either acute PCI with stent implantation within 24 hours after symptom onset or
- treatment with thrombolysis within 12 hours of symptom onset followed by PCI with stent implantation within 24 hours after thrombolysis.
Acute PCI / stent implantation has been successful (residual stenosis visually < 30% and TIMI flow >= 2).
At the time of inclusion patient does no longer require i.v. catecholamines or mechanical hemodynamic support (aortic balloon pump)
Significant regional wall motion abnormality in LV angiogram at the time of acute PCI (ejection fraction <= 45% on visual estimation).
Maximal CK elevation >= 400 U/l (measured at 37° C) with significant MB fraction > 6%
Age 18 - 80 Years
Written informed consent

Exclusion Criteria:

Regional wall motion abnormality outside the area involved in the index acute myocardial infarction.
Need to revascularize additional vessels, outside the infarct artery.
Arteriovenous malformations or aneurysms
Active infection (CRP > 10 mg/dl) now, or fever or diarrhea within last 4 weeks.
Chronic inflammatory disease
HIV infection or active hepatitis
Neoplastic disease without documented remission within the past 5 years.
Cerebrovascular insult within 3 months
Impaired renal function (creatinine > 2 mg/dl) at the time of cell therapy
Significant liver disease (GOT > 2x upper limit) or spontaneous INR > 1,5)
Anemia (hemoglobin < 8.5 mg/dl)
Platelet count < 100.000/µl
Hypersplenism
Known allergy or intolerance to clopidogrel, heparin or abciximab.
History of bleeding disorder
Gastrointestinal bleeding within 3 months
Major surgical procedure or traumata within 2 months
Uncontrolled hypertension
Pregnancy
Mental retardation
Previously performed stem / progenitor cell therapy
Participation in another clinical trial within the last 30 days.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00279175

Locations

Germany
Zentralklinik Bad Berka
Bad Berka, Germany, 99437
Kerckhoff Klinik
Bad Nauheim, Germany, 61231
Herz- und Diabeteszentrum NRW
Bad Oeynhausen, Germany, 32545
BG Kliniken Bergmannsheil
Bochum, Germany, 44789
Klinikum Lippe
Detmold, Germany, 32756
J. W. Goethe University Hospitals
Frankfurt, Germany, 60590
Rotes-Kreuz Krankenhaus - Kardiologisches Centrum
Frankfurt, Germany, 60316
Universitätsklinkum Giessen
Giessen, Germany, 35392
Parxis Schofer, Mathey und Partner
Hamburg, Germany, 22763
Universitätsklikum Homburg
Homburg/Saar, Germany, 66421
Klinikum Kassel
Kassel, Germany, 34125
Herzzentrum - Universität Leipzig
Leipzig, Germany, 04289
Herzzentrum Ludwigshafen
Ludwigshafen, Germany, 67073
Universitätsklinik Mainz
Mainz, Germany, 55131
Universitätsklinikum Mannheim
Mannheim, Germany, 68167
Zentralklinikum Suhl
Suhl, Germany, 98527
Switzerland
Universitätsspital Zürich
Zürich, Switzerland, 8091

Sponsors and Collaborators

Johann Wolfgang Goethe University Hospitals

Blutspendedienst Baden-Württemberg - Hessen

Guidant Corporation

Eli Lilly and Company

Investigators

Principal Investigator:	Andreas M Zeiher, MD	J. W. Goethe University Hospitals
Study Director:	Volker Schächinger, MD	J. W. Goethe University Hopspitals

More Information

Publications:

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.

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. 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 Nov 10; [Epub ahead of print]

Dill T, Schächinger V, Rolf A, Möllmann S, Thiele H, Tillmanns H, Assmus B, Dimmeler S, Zeiher AM, Hamm C. Intracoronary administration of bone marrow-derived progenitor cells improves left ventricular function in patients at risk for adverse remodeling after acute ST-segment elevation myocardial infarction: results of the Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction study (REPAIR-AMI) cardiac magnetic resonance imaging substudy. Am Heart J. 2009 Mar;157(3):541-7. Epub 2009 Jan 31.

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. Epub 2007 Jul 9.

Assmus B, Rolf A, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Tillmanns H, Yu J, Corti R, Mathey DG, Hamm CW, Süselbeck T, Tonn T, Dimmeler S, Dill T, Zeiher AM, Schächinger V; REPAIR-AMI Investigators. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail. 2010 Jan;3(1):89-96. Epub 2009 Dec 8.

Schachinger V, Tonn T, Dimmeler S, Zeiher AM. Bone-marrow-derived progenitor cell therapy in need of proof of concept: design of the REPAIR-AMI trial. Nat Clin Pract Cardiovasc Med. 2006 Mar;3 Suppl 1:S23-8.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rolf A, Assmus B, Schächinger V, Rixe J, Möllmann S, Möllmann H, Dimmeler S, Zeiher AM, Hamm CW, Dill T. Maladaptive hypertrophy after acute myocardial infarction positive effect of bone marrow-derived stem cell therapy on regional remodeling measured by cardiac MRI. Clin Res Cardiol. 2011 Nov;100(11):983-92. Epub 2011 Jun 17.

Assmus B, Tonn T, Seeger FH, Yoon CH, Leistner D, Klotsche J, Schächinger V, Seifried E, Zeiher AM, Dimmeler S. Red blood cell contamination of the final cell product impairs the efficacy of autologous bone marrow mononuclear cell therapy. J Am Coll Cardiol. 2010 Mar 30;55(13):1385-94.

Responsible Party:	Prof. Dr. Andreas M. Zeiher, Goethe University Hospitals
ClinicalTrials.gov Identifier:	NCT00279175 History of Changes
Other Study ID Numbers:	2/04, Paul-Ehrlich-Institute 1034/01, EudraCT 2006-000250-43
Study First Received:	January 18, 2006
Last Updated:	June 14, 2011
Health Authority:	Germany: Paul-Ehrlich-Institut

Keywords provided by Johann Wolfgang Goethe University Hospitals:

Acute myocardial infarction

Additional relevant MeSH terms:

Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis

Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on May 21, 2012