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

Nathan Mewton (1) , Thien T. Cung (2) , Olivier Morel (3, 4) , Guillaume Cayla (5) , Eric Bonnefoy-Cudraz (1) , Gilles Rioufol (1) , Denis Angoulvant (6) , Patrice Guerin (7) , Meyer Elbaz (8) , Nicolas Delarche (9) , Pierre Coste (8, 10) , Gérald Vanzetto (11) , Marc Metge (12) , Jean-François Aupetit (13) , Bernard Jouve (14) , Pascal Motreff (15) , Christophe Tron (16) , Jean-Noël Labeque (17) , Pierre G. Steg (18) , Yves Cottin (19, 20) , Grégoire Range (21) , Jerome Clerc (22) , Patrick Coussement (23) , Fabrice Prunier (24, 25) , Frederique Moulin (26) , Olivier Roth (27) , Loic Belle (28) , Phillipe Dubois (29) , Paul Barragan (30) , Martine Gilard (31) , Christophe Piot (32) , Patrice Colin (33) , Marie-Claude Morice (34) , Jean-Pierre Monassier (35) , Omar Ider (35) , Jean Luc P. Dubois-Randé (36) , Thierry Unterseeh (37) , Hervé Lebreton (38) , Thierry Beard (39) , Didier Blanchard (40) , Gilles Grollier (41) , Vincent Malquarti (42) , Patrick Staat (43) , Arnaud Sudre (44) , Magnus J. Hansson (45) , Eskil Elmer (45) , Inesse Boussaha (1) , Claire Jossan (1) , Anna Torner (46) , Marc Claeys (47) , David Garcia-Dorado (48) , Michel Ovize (49)

1 Hôpital Cardiovasculaire Louis Pradel
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 LBP - Laboratoire de Biophotonique et Pharmacologie - UMR 7213
4 Les Hôpitaux Universitaires de Strasbourg (HUS)
5 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
6 Cellules Dendritiques, Immunomodulation et Greffes
7 Hôpital Guillaume et René Laennec
8 Service Cardiologie [CHU Toulouse]
9 Centre hospitalier de Pau
10 Cardio - BORDEAUX - Department of Cardiology
11 Radiopharmaceutiques biocliniques
12 Centre Hospitalier Henri Duffaut (Avignon)
13 Hôpital Saint Joseph Saint Luc
14 Centre Hospitalier du Pays d'Aix
15 CHU Gabriel Montpied [Clermont-Ferrand]
16 Service de cardiologie [CHU Rouen]
17 Clinique Lafourcade [Bayonne]
18 Hôpital Bichat - Claude Bernard
19 LNC - Lipides - Nutrition - Cancer (U866)
20 CHU Dijon
21 Centre Hospitalier Général
22 Centre Hospitalier Compiègne-Noyon
23 Hospital St-Jan Bruges
24 Service de Cardiologie
25 PMRM - Laboratoire de Protection et Remodelage du Myocarde
26 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
27 CH E.Muller Mulhouse - Centre Hospitalier Emile Muller [Mulhouse]
28 Service de Cardiologie
29 CHU Henri Mondor
30 Polyclinique Les Fleurs
31 ORPHY (EA 4324) - Optimisation des régulations physiologiques
32 IGF - Institut de Génomique Fonctionnelle
33 Clinique Esquirol St Hilaire
34 Hôpital Privé Jacques Cartier [Massy]
35 Clinique du Diaconat
36 Grand Hopital de Charleroi
37 Centre Hospitalier Privé Claude Galien - Ramsay Santé
38 LTSI - Laboratoire Traitement du Signal et de l'Image
39 Polyclinique de l'Ormeau
40 Pôle Cardiologie Interventionnelle / Coro-scanner / IRM Cardiaque
41 CHU Caen
42 Clinique de la Sauvegarde [Lyon]
43 Clinique du Tonkin
44 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
45 Lund University [Lund]
46 Scandinavian Development Services AB
47 Universiteit Antwerpen = University of Antwerpen [Antwerpen]
48 Vall d'Hebron University Hospital [Barcelona]
49 Cardioprotection

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 the minutes 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

Domains: Life Sciences [q-bio]; Bioengineering

Nathan Mewton, Thien T. Cung, Olivier Morel, Guillaume Cayla, Eric Bonnefoy-Cudraz, et al.. Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial). American Heart Journal, 2015, 169 (6), pp.758--766.e6. ⟨10.1016/j.ahj.2015.02.020⟩. ⟨hal-01260554⟩