The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction: rationale and design of the BAMI trial
Language English Country Great Britain, England Media print-electronic
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
28948706
PubMed Central
PMC6607485
DOI
10.1002/ejhf.829
Knihovny.cz E-resources
- Keywords
- BAMI, Bone marrow-derived mononuclear cells, Cardiac regeneration, Cardiovascular disease, Cell therapy, Heart failure, Myocardial infarction,
- MeSH
- Echocardiography MeSH
- Ventricular Function, Left physiology MeSH
- ST Elevation Myocardial Infarction diagnosis mortality therapy MeSH
- Humans MeSH
- Survival Rate trends MeSH
- Cause of Death trends MeSH
- Bone Marrow Transplantation methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Geographicals
- Europe epidemiology MeSH
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
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
University College London London UK
University Hospitals Leuven Leuven Belgium
Vall d'Hebron University Hospital and Research Institute Universitat Autònoma de Barcelona Spain
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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
ClinicalTrials.gov
NCT01569178