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Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial)

Mewton, Nathan; Cung, Thien T.; Morel, Olivier; Cayla, Guillaume; Bonnefoy-Cudraz, Eric; Rioufol, Gilles; Angoulvant, Denis; Guerin, Patrice; Elbaz, Meyer and Delarche, Nicolas, et al. (2015) In American Heart Journal 169(6). p.6-766
Abstract
Background Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. Methods CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial... (More)
Background Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. Methods CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow <= 1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1: 1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in theminutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. Results Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. Conclusions The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up. (Less)
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Contribution to journal
publication status
published
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in
American Heart Journal
volume
169
issue
6
pages
6 - 766
publisher
Mosby
external identifiers
  • wos:000355213300003
  • pmid:26027612
  • scopus:84930147019
ISSN
1097-6744
DOI
10.1016/j.ahj.2015.02.020
language
English
LU publication?
yes
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259b90c6-94ad-4874-bad5-584c73ffa09e (old id 7410529)
date added to LUP
2015-07-03 07:02:12
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2017-10-01 03:32:32
@article{259b90c6-94ad-4874-bad5-584c73ffa09e,
  abstract     = {Background Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. Methods CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow &lt;= 1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1: 1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in theminutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. Results Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. Conclusions The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.},
  author       = {Mewton, Nathan and Cung, Thien T. and Morel, Olivier and Cayla, Guillaume and Bonnefoy-Cudraz, Eric and Rioufol, Gilles and Angoulvant, Denis and Guerin, Patrice and Elbaz, Meyer and Delarche, Nicolas and Coste, Pierre and Vanzetto, Gerald and Metge, Marc and Aupetit, Jean-Francois and Jouve, Bernard and Motreff, Pascal and Tron, Christophe and Labeque, Jean-Noel and Steg, Pierre G. and Cottin, Yves and Range, Gregoire and Clerc, Jerome and Coussement, Patrick and Prunier, Fabrice and Moulin, Frederique and Roth, Olivier and Belle, Loic and Dubois, Phillipe and Barragan, Paul and Gilard, Martine and Piot, Christophe and Colin, Patrice and Morice, Marie-Claude and Monassier, Jean-Pierre and Ider, Omar and Dubois-Rande, Jean Luc P. and Unterseeh, Thierry and Lebreton, Herve and Beard, Thierry and Blanchard, Didier and Grollier, Gilles and Malquarti, Vincent and Staat, Patrick and Sudre, Arnaud and Hansson, Magnus and Elmer, Eskil and Boussaha, Inesse and Jossan, Claire and Torner, Anna and Claeys, Marc and Garcia-Dorado, David and Ovize, Michel},
  issn         = {1097-6744},
  language     = {eng},
  number       = {6},
  pages        = {6--766},
  publisher    = {Mosby},
  series       = {American Heart Journal},
  title        = {Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial)},
  url          = {http://dx.doi.org/10.1016/j.ahj.2015.02.020},
  volume       = {169},
  year         = {2015},
}