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

Myocardial Infarction Clinical Trial

Official title:

Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Myocardial Infarction (REPAIR - AMI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00279175
• Other study ID #: 2/04
• Secondary ID: Paul-Ehrlich-Ins
• Status: Completed
• Phase: Phase 3
• First received: January 18, 2006
• Last updated: September 19, 2012
• Start date: April 2004
• Est. completion date: December 2010

Study information

• Verified date: September 2012
• Source: Johann Wolfgang Goethe University Hospitals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 204
• Est. completion date: December 2010
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

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

• Infarction
• Myocardial Infarction

Intervention

Biological:
• Intracoronary infusion of enriched bone marrow-derived progenitor cells

• Placebo medium supplemented with autologous serum

Locations

Country	Name	City	State
Germany	Zentralklinik Bad Berka	Bad Berka
Germany	Kerckhoff Klinik	Bad Nauheim
Germany	Herz- und Diabeteszentrum NRW	Bad Oeynhausen
Germany	BG Kliniken Bergmannsheil	Bochum
Germany	Klinikum Lippe	Detmold
Germany	J. W. Goethe University Hospitals	Frankfurt
Germany	Rotes-Kreuz Krankenhaus - Kardiologisches Centrum	Frankfurt
Germany	Universitätsklinkum Giessen	Giessen
Germany	Parxis Schofer, Mathey und Partner	Hamburg
Germany	Universitätsklikum Homburg	Homburg/Saar
Germany	Klinikum Kassel	Kassel
Germany	Herzzentrum - Universität Leipzig	Leipzig
Germany	Herzzentrum Ludwigshafen	Ludwigshafen
Germany	Universitätsklinik Mainz	Mainz
Germany	Universitätsklinikum Mannheim	Mannheim
Germany	Zentralklinikum Suhl	Suhl
Switzerland	Universitätsspital Zürich	Zürich

Sponsors (5)

Lead Sponsor	Collaborator
A. M. Zeiher	Blutspendedienst Baden-Württemberg - Hessen, Eli Lilly and Company, Guidant Corporation, Johann Wolfgang Goethe University Hospitals

Countries where clinical trial is conducted

Germany,  Switzerland, 

References & Publications (6)

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 admi — View Citation

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 a — 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 progen — 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 my — 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 clin — View Citation

Schächinger 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in global left ventricular function in quantitative LV angiography after 4 months.	absolute delta LVEF (%)	baseline to 4 months	No
Secondary	Primary endpoint in patients without restenosis.	absolute delta LVEF (%)	baseline to 4 months	Yes
Secondary	Improvement of regional wall motion in infarct area		baseline to 4 months	No
Secondary	Reduction of LV end-systolic volume		baseline to 4 months	No
Secondary	Major adverse cardiac events (MACE)		at 4, 12 and 60 months	Yes
Secondary	Rehospitalization due to heart failure.		4, 12, 60 months	Yes
Secondary	NYHA status after 12 months		12 months	No
Secondary	Amendment for extended follow up after 2 and 5 years:		24 and 60 months	Yes
Secondary	outcomes in major adverse cardiac events (MACE)		4, 12, 60 months	Yes
Secondary	Rehospitalization due to heart failure		4, 12, 60 months	Yes
Secondary	NYHA status		4, 12, 60 months	No
Secondary	patients in MRI subgroup: improvement in left ventricular function		4, 12, 60 months	Yes