Over the past 13 years bone marrow-derived mononuclear cells (BM-MNCs) have been widely investigated for clinical efficacy in patients following acute myocardial infarction (AMI). These early phase II trials have used various surrogate markers to judge efficacy and, although promising, the results have been inconsistent. The phase III BAMI trial has therefore been designed to demonstrate that intracoronary infusion of BM-MNCs is safe and will significantly reduce the time to first occurrence of all-cause death in patients with reduced left ventricular ejection fraction after successful reperfusion for ST-elevation AMI (powered with the aim of detecting a 25% reduction in all-cause mortality). This is a multinational, multicentre, randomized, open-label, controlled, parallel-group phase III study aiming to enrol approximately 3000 patients in 11 European countries with at least 17 sites. Eligible patients who have impaired left ventricular ejection (≤45%) following successful reperfusion for AMI will be randomized to treatment or control group in a 1:1 ratio. The treatment group will receive intracoronary infusion of BM-MNCs 2-8 days after successful reperfusion for AMI added on top of optimal standard of care. The control group will receive optimal standard of care. The primary endpoint is time from randomization to all-cause death. The BAMI trial is pivotal and the largest trial to date of BM-MNCs in patients with impaired left ventricular function following AMI. The aim of the trial is to provide a definitive answer as to whether BM-MNCs reduce all-cause mortality in this group of patients.

Assistance Publique Hopitaux de Paris University Paris Descartes Paris France

Barts Heart Centre London UK

Catholic University of the Sacred Heart Rome Italy

Celyad SA Mont Saint Guibert Belgium

Faculty Hospital and Masaryk University Brno Czech Republic

Hospital General Universitario Gregorio Marañón Madrid Spain

ICICORELAB Hospital Clínico Universitario Valladolid Spain

Johann Wolfgang Goethe University Frankfurt and DRK Blutspendedienst BaWüHe Germany

Johann Wolfgang Goethe University Frankfurt Germany

King's College Hospital London UK

KU Leuven University of Leuven and Universiteit Hasselt 1 BioStat Leuven Belgium

Kuopio University Hospital and University of Eastern Finland Kuopio Finland

Medical University of Silesia Katowice Poland

Queen Mary University of London London UK

Rigshospitalet University of Copenhagen Copenhagen Denmark

t2cure Frankfurt Germany

University College London London UK

University Hospitals Leuven Leuven Belgium

Vall d'Hebron University Hospital and Research Institute Universitat Autònoma de Barcelona Spain

VZW Cardiovascular Research Center Aalst Aalst Belgium

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Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartmann F, Gersh BJ, Pocock SJ, Dangas G, Wong SC, Fahy M, Parise H, Mehran R; HORIZONS‐AMI Trial Investigators . Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel‐eluting stents versus bare‐metal stents in acute myocardial infarction (HORIZONS‐AMI): final 3‐year results from a multicentre, randomised controlled trial. Lancet 2011;377:2193–2204. PubMed

Setoguchi S, Glynn RJ, Avorn J, Mittleman MA, Levin R, Winkelmayer WC. Improvements in long‐term mortality after myocardial infarction and increased use of cardiovascular drugs after discharge: a 10‐year trend analysis. J Am Coll Cardiol 2008;51:1247–1254. PubMed

Keeley EC, Boura JA, Grines CL. Comparison of primary and facilitated percutaneous coronary interventions for ST‐elevation myocardial infarction: quantitative review of randomised trials. Lancet 2006;367:579–588. PubMed

Ng VG, Lansky AJ, Meller S, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie B, Shah R, Mehran R, Stone GW. The prognostic importance of left ventricular function in patients with ST‐segment elevation myocardial infarction: the HORIZONS‐AMI trial. Eur Heart J Acute Cardiovasc Care 2014;3:67–77. PubMed PMC

Kelly DJ, Gershlick T, Witzenbichler B, Guagliumi G, Fahy M, Dangas G, Mehran R, Stone GW. Incidence and predictors of heart failure following percutaneous coronary intervention in ST‐segment elevation myocardial infarction: the HORIZONS‐AMI trial. Am Heart J 2011;162:663–670. PubMed

Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal‐Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701–705. PubMed

Jeevanantham V, Butler M, Saad A, Abdel‐Latif A, Zuba‐Surma EK, Dawn B. Adult bone marrow cell therapy improves survival and induces long‐term improvement in cardiac parameters: a systematic review and meta‐analysis. Circulation 2012;126:551–568. PubMed PMC

Martin‐Rendon E, Brunskill SJ, Hyde CJ, Stanworth SJ, Mathur A, Watt SM. Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review. Eur Heart J 2008;29:1807–1818. PubMed

Bartunek J, Dimmeler S, Drexler H, Fernandez‐Aviles F, Galinanes M, Janssens S, Martin J, Mathur A, Menasche P, Priori S, Strauer B, Tendera M, Wijns W, Zeiher A. The consensus of the task force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for repair of the heart. Eur Heart J 2006;27:1338–1340. PubMed

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;355:1210–1221. PubMed

Lan KK, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika 1983;70:659–663.

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;3:89–96. PubMed

Reffelmann T, Konemann S, Kloner RA. Promise of blood‐ and bone marrow‐derived stem cell transplantation for functional cardiac repair: putting it in perspective with existing therapy. J Am Coll Cardiol 2009;53:305–308. PubMed

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;27:2775–2783. PubMed

Seeger FH, Rasper T, Fischer A, Muhly‐Reinholz M, Hergenreider E, Leistner DM, Sommer K, Manavski Y, Henschler R, Chavakis E, Assmus B, Zeiher AM, Dimmeler S. Heparin disrupts the CXCR4/SDF‐1 axis and impairs the functional capacity of bone marrow‐derived mononuclear cells used for cardiovascular repair. Circ Res 2012;111:854–862. PubMed

The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction: the BAMI trial

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NCT01569178