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Original Investigation
August 2016

Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac ArrestThe CYRUS Randomized Clinical Trial

Author Affiliations
  • 1Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Réanimation Médicale, Lyon, France
  • 2Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1060, Carmen, Equipe Cardioprotection, Lyon, France
  • 3Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France
  • 4Hospices Civils de Lyon, Service d’Aide Médicale Urgente 69, Lyon, France
  • 5Centre Hospitalier Universitaire de Saint-Etienne, Service d’Aide Médicale Urgente 42A, Saint-Etienne, France
  • 6Hospices Civils de Lyon, Hôpital Louis Pradel, Explorations Fonctionnelles Cardiovasculaires et Centre d’Investigation Clinique de Lyon, Lyon, France
  • 7Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service de Biostatistique, Lyon, France
  • 8Centre National de la Recherche Scientifique Unité Mixte de Recherche 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
  • 9Centre Hospitalier Universitaire de Saint-Etienne, Hôpital Nord, Service de Réanimation Polyvalente, Saint-Etienne, France
  • 10Centre Hospitalier de Bourg-en-Bresse, Hôpital Fleyriat, Service d’Aide Médicale Urgente 01, Bourg-en-Bresse, France
  • 11Centre Hospitalier de Bourg-en-Bresse, Hôpital Fleyriat, Service de Réanimation Polyvalente, Bourg-en-Bresse, France
  • 12Centre Hospitalier Universitaire de Dijon, Hôpital François Mitterand, Service de Réanimation Médicale, Dijon, France
  • 13Centre Hospitalier Universitaire de Dijon, Service d’Aide Médicale Urgente 21, Dijon, France
  • 14Centre Hospitalier de Roanne, Service d’Aide Médicale Urgente 42B, Roanne, France
  • 15Centre Hospitalier de Roanne, Service de Réanimation et Soins Continus, Roanne, France
  • 16Centre Hospitalier Métropole Savoie, Service d’Aide Médicale Urgente 73, Chambéry, France
  • 17Centre Hospitalier Métropole Savoie, Service de Réanimation Polyvalente, Chambéry, France
  • 18Centre Hospitalier de Villefranche-sur-Saône, Service Mobile d’Urgence et de Réanimation de Villefranche-sur-Saône, Villefranche-sur-Saône, France
  • 19Centre Hospitalier de Villefranche-sur-Saône, Service de Réanimation, Villefranche-sur-Saône, France
  • 20Centre Hospitalier d’Ardèche Nord, Service Mobile d’Urgence et de Réanimation d’Annonay, Annonay, France
  • 21Centre Hospitalier Régional Universitare, Service d’Aide Médicale Urgente 54, Nancy, France
  • 22Centre Hospitalier Universitaire de Nîmes, Pôle Anesthésie Réanimation Douleur Urgences, Nîmes, France
JAMA Cardiol. 2016;1(5):557-565. doi:10.1001/jamacardio.2016.1701

Importance  Experimental evidence suggests that cyclosporine prevents postcardiac arrest syndrome by attenuating the systemic ischemia reperfusion response.

Objective  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.

Design, Setting, and Participants  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.

Interventions  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).

Main Outcomes and Measures  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.

Results  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).

Conclusion and Relevance  In patients presenting with nonshockable cardiac rhythm after OHCA, cyclosporine does not prevent early multiple organ failure.

Trial Registration  clinicaltrials.gov Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37