Clinical trial NCT00279175: REPAIR-AMI: Intracoronary Progenitor Cells in Acute Myocardial Infarction (AMI)
Official title: Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Myocardial Infarction (REPAIR - AMI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Infarction
Keywords: Acute myocardial infarction
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
Collaborators: name: Johann Wolfgang Goethe University Hospital
name: Blutspendedienst Baden-Württemberg - Hessen
name: Guidant Corporation
name: Eli Lilly and Company
First posted: 2006-01-19
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Change in global left ventricular function in quantitative LV angiography after 4 months.
timeFrame: baseline to 4 months
Secondary outcomes:
measure: Primary endpoint in patients without restenosis.
timeFrame: baseline to 4 months
measure: Improvement of regional wall motion in infarct area
timeFrame: baseline to 4 months
measure: Reduction of LV end-systolic volume
timeFrame: baseline to 4 months
measure: Major adverse cardiac events (MACE)
timeFrame: at 4, 12 and 60 months
measure: Rehospitalization due to heart failure.
timeFrame: 4, 12, 60 months
measure: NYHA status after 12 months
timeFrame: 12 months
measure: Amendment for extended follow up after 2 and 5 years:
timeFrame: 24 and 60 months
measure: outcomes in major adverse cardiac events (MACE)
timeFrame: 4, 12, 60 months
measure: Rehospitalization due to heart failure
timeFrame: 4, 12, 60 months
measure: NYHA status
timeFrame: 4, 12, 60 months
measure: patients in MRI subgroup: improvement in left ventricular function
timeFrame: 4, 12, 60 months
Other outcomes:
Locations:
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW
city: Bochum
country: Germany
facility: BG Kliniken Bergmannsheil
city: Detmold
country: Germany
facility: Klinikum Lippe
city: Frankfurt
country: Germany
facility: Rotes-Kreuz Krankenhaus - Kardiologisches Centrum
city: Frankfurt
country: Germany
facility: J. W. Goethe University Hospitals
city: Giessen
country: Germany
facility: Universitätsklinkum Giessen
city: Hamburg
country: Germany
facility: Parxis Schofer, Mathey und Partner
city: Homburg/Saar
country: Germany
facility: Universitätsklikum Homburg
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Leipzig
country: Germany
facility: Herzzentrum - Universität Leipzig
city: Ludwigshafen
country: Germany
facility: Herzzentrum Ludwigshafen
city: Mainz
country: Germany
facility: Universitätsklinik Mainz
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: Suhl
country: Germany
facility: Zentralklinikum Suhl
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: J. W. Goethe University Hospitals
name: Andreas M Zeiher, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: J. W. Goethe University Hopspitals
name: Volker Schächinger, MD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1038/ncpcardio0441.
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.
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.
citation: Dill T, Schachinger V, Rolf A, Mollmann 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. doi: 10.1016/j.ahj.2008.11.011. Epub 2009 Jan 31.
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.
citation: Assmus B, Rolf A, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Tillmanns H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Tonn T, Dimmeler S, Dill T, Zeiher AM, Schachinger 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. doi: 10.1161/CIRCHEARTFAILURE.108.843243. Epub 2009 Dec 8.
citation: Rolf A, Assmus B, Schachinger V, Rixe J, Mollmann S, Mollmann 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. doi: 10.1007/s00392-011-0330-3. Epub 2011 Jun 17.
citation: Assmus B, Tonn T, Seeger FH, Yoon CH, Leistner D, Klotsche J, Schachinger 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. doi: 10.1016/j.jacc.2009.10.059.