Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction - MiHeart/AMI study

Hans F R Dohmann, Suzana A Silva, André L S Sousa, Alcione M S Braga, Rodrigo V C Branco, Andréa F Haddad, Mônica A Oliveira, Rodrigo C Moreira, Fabio A A Tuche, Cíntia M Peixoto, Bernardo R Tura, Radovan Borojevic, Jorge P Ribeiro, José C Nicolau, Antonio C Nóbrega, Antonio C C Carvalho, Hans F R Dohmann, Suzana A Silva, André L S Sousa, Alcione M S Braga, Rodrigo V C Branco, Andréa F Haddad, Mônica A Oliveira, Rodrigo C Moreira, Fabio A A Tuche, Cíntia M Peixoto, Bernardo R Tura, Radovan Borojevic, Jorge P Ribeiro, José C Nicolau, Antonio C Nóbrega, Antonio C C Carvalho

Abstract

Background: Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls.

Methods: A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 x 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum).

Implications: Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required.

Trial register: This trial is registered at the NIH registry under the number NCT00350766.

References

    1. Wu AH, Parsons L, Every NR, Bates ER. J Am Coll Cardiol. 2002;40:1389–94. doi: 10.1016/S0735-1097(02)02173-3.
    1. McMurray JJ, Stewart S. Heart. 2000;83:596–602. doi: 10.1136/heart.83.5.596.
    1. Morbidade Hospitalar do SUS – Por Local de Internação – Brasil. 2007. cited 2008 Feb 26.
    1. Strauer BE, Brehm M, Zeus T, Gattermann N, Hernandez A, Sorg RV, Kogler G, Wernet P. Dtsch Med Wochenschr. 2001;126:932–938. doi: 10.1055/s-2001-16579-1.
    1. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Circulation. 2002;106:3009–17. doi: 10.1161/.
    1. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. J Am Coll Cardiol. 2004;44:1690–9. doi: 10.1016/j.jacc.2004.08.014.
    1. Dobert N, Britten M, Assmus B, Berner U, Menzel C, Lehmann R, Hamscho N, Schachinger V, Dimmeler S, Zeiher AM, Grunwald F. Eur J Nucl Med Mol Imaging. 2004;31:1146–51. doi: 10.1007/s00259-004-1490-4.
    1. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H. Lancet. 2004;364:141–8. doi: 10.1016/S0140-6736(04)16626-9.
    1. Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, Zhang JJ, Chunhua RZ, Liao LM, Lin S, Sun JP. Am J Cardiol. 2004;94:92–5. doi: 10.1016/j.amjcard.2004.03.034.
    1. Ruan W, Pan CZ, Huang GQ, Li YL, Ge JB, Shu XH. Chin Med J (Engl) 2005;118:1175–81.
    1. Tura BR, Martino HF, Gowdak LH, Dos Santos RR, Dohmann HF, Krieger JE, Feitosa G, Vilas-Boas F, Oliveira SA, Silva SA, Bozza AZ, Borojevic R, de Carvalho AC. Trials. 2007;8:2. doi: 10.1186/1745-6215-8-2.
    1. Coutinho LH, Gilleece MH, De Wynter EA, et al. In: Haemopoiesis: A Practical Approach. Testa NG, Molineux G, editor. Oxford University Press, New York; 1993. pp. 84–85.
    1. Castro-Malaspina H, Gay RE, Resnick G, Kapoor N, Meyers P, Chiarieri D, McKenzie S, Broxmeyer HE, Moore MA. Blood. 1980;56:289–301.
    1. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS. Circulation. 2002;105:539–42. doi: 10.1161/hc0402.102975.
    1. Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, Kalantzi M, Herbots L, Sinnaeve P, Dens J, Maertens J, Rademakers F, Dymarkowski S, Gheysens O, Van Cleemput J, Bormans G, Nuyts J, Belmans A, Mortelmans L, Boogaerts M, Van de Werf F. Lancet. 2006;367:113–21. doi: 10.1016/S0140-6736(05)67861-0.
    1. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grogaard HK, Bjornerheim R, Brekke M, Muller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K. N Engl J Med. 2006;355:1199–209. doi: 10.1056/NEJMoa055706.
    1. Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, Kogler G, Wernet P. Circulation. 2002;106:1913–8. doi: 10.1161/01.CIR.0000034046.87607.1C.
    1. Bartunek J, Vanderheyden M, Vandekerckhove B, Mansour S, De Bruyne B, De Bondt P, Van Haute I, Lootens N, Heyndrickx G, Wijns W. Circulation. 2005;112:I178–83.
    1. 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. Eur Heart J. 2006;27:2775–83. doi: 10.1093/eurheartj/ehl388.

Source: PubMed

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