title: Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest: The CYRUS Randomized Clinical Trial.
abstract: Experimental evidence suggests that cyclosporine prevents postcardiac arrest syndrome by attenuating the systemic ischemia reperfusion response.
  
  
  
  To determine whether early administration of cyclosporine at the time of resuscitation in patients with out-of-hospital cardiac arrest (OHCA) would prevent multiple organ failure.
  
  
  
  A multicenter, single-blind, randomized clinical trial was conducted from June 22, 2010, to March 13, 2013 (Cyclosporine A in Out-of-Hospital Cardiac Arrest Resuscitation [CYRUS]). Sixteen intensive care units in 7 university-affiliated hospitals and 9 general hospitals in France participated. A total of 6758 patients who experienced nonshockable OHCA (ie, asystole or pulseless electrical activity) were assessed for eligibility. Analyses were performed according to the intention-to-treat analysis.
  
  
  
  Patients received an intravenous bolus injection of cyclosporine, 2.5 mg/kg, at the onset of advanced cardiovascular life support (cyclosporine group) or no additional intervention (control group).
  
  
  
  The primary end point was the Sequential Organ Failure Assessment (SOFA) score, assessed 24 hours after hospital admission, which ranges from 0 to 24 (with higher scores indicating more severe organ failure). Secondary end points included survival at 24 hours, hospital discharge, and favorable neurologic outcome at discharge.
  
  
  
  Of the 6758 patients screened, 794 were included in intention-to-treat analysis (cyclosporine, 400; control, 394). The median (interquartile range [IQR]) ages were 63.0 (54.0-71.8) years for the cyclosporine group and 66.0 (57.0-74.0) years for the control group. The cohorts included 293 men (73.3%) in the treatment group and 288 men (73.1%) in the control group. At 24 hours after hospital admission, the SOFA score was not significantly different between the cyclosporine (median, 10.0; IQR, 7.0-13.0) and the control (median, 11.0; IQR, 7.0-15.0) groups. Survival was not significantly different between the 98 (24.5%) cyclosporine vs 101 (25.6%) control patients at hospital admission (adjusted odds ratio [aOR], 0.94; 95% CI, 0.66-1.34), at 24 hours for 67 (16.8%) vs 62 (15.7%) patients (aOR, 1.08; 95% CI, 0.71-1.63), and at hospital discharge for 10 (2.5%) vs 5 (1.3%) patients (aOR, 2.00; 95% CI, 0.61-6.52). Favorable neurologic outcome at discharge was comparable between the cyclosporine and control groups: 7 (1.8%) vs 5 (1.3%) patients (aOR, 1.39; 95% CI, 0.39-4.91).
  
  
  
  In patients presenting with nonshockable cardiac rhythm after OHCA, cyclosporine does not prevent early multiple organ failure.
  
  
  
  clinicaltrials.gov Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37.
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Réanimation Médicale, Lyon, France2Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1060, Carmen, Equipe Cardioprotection, Lyon, France3Université de Lyon, Uni.
authors.forename: Laurent
authors.initials: L
authors.lastname: Argaud
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Réanimation Médicale, Lyon, France2Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1060, Carmen, Equipe Cardioprotection, Lyon, France3Université de Lyon, Uni.
authors.forename: Martin
authors.initials: M
authors.lastname: Cour
authors.affiliation: Hospices Civils de Lyon, Service d'Aide Médicale Urgente 69, Lyon, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dubien
authors.affiliation: Centre Hospitalier Universitaire de Saint-Etienne, Service d'Aide Médicale Urgente 42A, Saint-Etienne, France.
authors.forename: François
authors.initials: F
authors.lastname: Giraud
authors.affiliation: Hospices Civils de Lyon, Hôpital Louis Pradel, Explorations Fonctionnelles Cardiovasculaires et Centre d'Investigation Clinique de Lyon, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Jossan
authors.affiliation: Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France7Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service de Biostatistique, Lyon, France8Centre National de la Recherche Scientifique Unité Mixte de Recherche 5558, Laboratoire de Bio.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Riche
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Réanimation Médicale, Lyon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Hernu
authors.affiliation: Centre Hospitalier Universitaire de Saint-Etienne, Hôpital Nord, Service de Réanimation Polyvalente, Saint-Etienne, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Darmon
authors.affiliation: Centre Hospitalier de Bourg-en-Bresse, Hôpital Fleyriat, Service d'Aide Médicale Urgente 01, Bourg-en-Bresse, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Poncelin
authors.affiliation: Centre Hospitalier de Bourg-en-Bresse, Hôpital Fleyriat, Service de Réanimation Polyvalente, Bourg-en-Bresse, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Tchénio
authors.affiliation: Centre Hospitalier Universitaire de Dijon, Hôpital François Mitterand, Service de Réanimation Médicale, Dijon, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Quenot
authors.affiliation: Centre Hospitalier Universitaire de Dijon, Service d'Aide Médicale Urgente 21, Dijon, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Freysz
authors.affiliation: Centre Hospitalier de Roanne, Service d'Aide Médicale Urgente 42B, Roanne, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Kamga
authors.affiliation: Centre Hospitalier de Roanne, Service de Réanimation et Soins Continus, Roanne, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Beuret
authors.affiliation: Centre Hospitalier Métropole Savoie, Service d'Aide Médicale Urgente 73, Chambéry, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Usseglio
authors.affiliation: Centre Hospitalier Métropole Savoie, Service de Réanimation Polyvalente, Chambéry, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Badet
authors.affiliation: Centre Hospitalier de Villefranche-sur-Saône, Service Mobile d'Urgence et de Réanimation de Villefranche-sur-Saône, Villefranche-sur-Saône, France.
authors.forename: Bastien
authors.initials: B
authors.lastname: Anette
authors.affiliation: Centre Hospitalier de Villefranche-sur-Saône, Service de Réanimation, Villefranche-sur-Saône, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chaulier
authors.affiliation: Centre Hospitalier d'Ardèche Nord, Service Mobile d'Urgence et de Réanimation d'Annonay, Annonay, France.
authors.forename: Emel
authors.initials: E
authors.lastname: Alasan
authors.affiliation: Centre Hospitalier Régional Universitare, Service d'Aide Médicale Urgente 54, Nancy, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Sadoune
authors.affiliation: Centre Hospitalier Universitaire de Nîmes, Pôle Anesthésie Réanimation Douleur Urgences, Nîmes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Bobbia
authors.affiliation: Centre Hospitalier Universitaire de Saint-Etienne, Service d'Aide Médicale Urgente 42A, Saint-Etienne, France9Centre Hospitalier Universitaire de Saint-Etienne, Hôpital Nord, Service de Réanimation Polyvalente, Saint-Etienne, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Zéni
authors.affiliation: Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France4Hospices Civils de Lyon, Service d'Aide Médicale Urgente 69, Lyon, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Gueugniaud
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Réanimation Médicale, Lyon, France3Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Robert
authors.affiliation: Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France7Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service de Biostatistique, Lyon, France8Centre National de la Recherche Scientifique Unité Mixte de Recherche 5558, Laboratoire de Bio.
authors.forename: Pascal
authors.initials: P
authors.lastname: Roy
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1060, Carmen, Equipe Cardioprotection, Lyon, France3Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France6Hospices Civils de Lyon, Hôpital Louis Pradel, Explo.
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
mesh_terms: D000368:Aged; D016887:Cardiopulmonary Resuscitation; D016572:Cyclosporine / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000517:prevention & control*; D058687:Out-of-Hospital Cardiac Arrest / Q000150:complications*; D016037:Single-Blind Method
chemical_list: D004791:Enzyme Inhibitors; D016572:Cyclosporine