title: Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial.
abstract: Preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs.
  
  
  
  The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial.
  
  
  
  The authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects.
  
  
  
  In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01).
  
  
  
  In patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583).
authors.affiliation: Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Paris, France; INSERM U970 (team 4), Parisian Cardiovascular Research Center, Paris Descartes University, Paris, France. Electronic address: alain.cariou@aphp.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Cariou
authors.affiliation: Medical Intensive Care Unit, Lariboisière Hospital (APHP) and INSERM U942, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Deye
authors.affiliation: Paris Descartes University, Paris, France; SAMU 75, Necker Hospital (AP-HP), Paris, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Vivien
authors.affiliation: SAMU 78, Centre Hospitalier de Versailles, Versailles, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Richard
authors.affiliation: Medical ICU, CHU Dupuytren, Limoges, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pichon
authors.affiliation: SAMU 87 and CHU Dupuytren, Limoges, France.
authors.forename: Angèle
authors.initials: A
authors.lastname: Bourg
authors.affiliation: SAMU 94, Henri Mondor Hospital (APHP), Créteil, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Huet
authors.affiliation: CHU de Caen, Pôle Réanimations, Anesthésie, SAMU, Caen, Caen, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Buleon
authors.affiliation: SAMU 54, CHU de Nancy, Nancy, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Frey
authors.affiliation: Réanimation Médicale et de Médecine Hyperbare, CHU d'Angers, Angers, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.affiliation: Medical ICU, Centre Hospitalier de Versailles, Versailles, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Legriel
authors.affiliation: SAMU 45, Hôpital de La Source, Orléans, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Narcisse
authors.affiliation: Medical-Surgical Intensive Care Unit, Hôpital de La Source, Centre Hospitalier Regional d'Orléans, Orléans, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Mathonnet
authors.affiliation: Medical ICU, CHU de Nancy, Nancy, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cravoisy
authors.affiliation: Medical ICU, François Rabelais University, Inserm U1100 and CRICS group, Tours, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Dequin
authors.affiliation: Emergency Department and SAMU 59, Lille University Hospital, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Wiel
authors.affiliation: Medical ICU, Hôpital Henri Mondor (APHP), Créteil, France.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Razazi
authors.affiliation: CHU de Caen, Department of Medical Intensive Care, Caen, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Daubin
authors.affiliation: Service de Réanimation Médicale Brabois, CHU de Nancy, Vandœuvres-les-Nancy, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Kimmoun
authors.affiliation: INSERM U970 (team 4), Parisian Cardiovascular Research Center, Paris Descartes University, Paris, France; SAMU 75, Necker Hospital (AP-HP), Paris, France; Intensive Care Unit, Necker University Hospital (APHP), Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Lamhaut
authors.affiliation: SAMU 75, Necker Hospital (AP-HP), Paris, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Marx
authors.affiliation: SMUR & Surgical Intensive Care, Lariboisière University Hospital (APHP) and Paris 7 University Denis Diderot, Paris, France.
authors.forename: Didier Payen
authors.initials: DP
authors.lastname: de la Garanderie
authors.affiliation: SMUR Pitié-Salpêtrière (APHP), Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ecollan
authors.affiliation: Medical Intensive Care Unit, INSERM, UMRS-1166, Université Pierre et Marie Curie, iCAN, Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié-Salpêtrière (APHP), Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Combes
authors.affiliation: Paris Descartes University, Paris, France; INSERM U970 (team 4), Parisian Cardiovascular Research Center, Paris Descartes University, Paris, France; Cardiology Department, Cochin University Hospital (APHP), Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Spaulding
authors.affiliation: Clinical Trial Unit, Central Pharmacy, APHP, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Barat
authors.affiliation: Biostatistics and Epidemiology Unit, Hôtel-Dieu Hospital (APHP, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Ben Boutieb
authors.affiliation: Paris Descartes University, Paris, France; Biostatistics and Epidemiology Unit, Hôtel-Dieu Hospital (APHP, Paris, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Coste
authors.affiliation: Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Paris, France.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Chiche
authors.affiliation: Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pène
authors.affiliation: Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.affiliation: Paris Descartes University, Paris, France; Clinical Research Unit, Paris Centre and Paris Descartes University, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.affiliation: Paris Descartes University, Paris, France; Hematology Department, Necker Hospital (APHP), Imagine institute, INSERM U1123 CNRS erl 8654, Labex des Globules Rouges Grex, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Paris Descartes University, Paris, France; SAMU 75, Necker Hospital (AP-HP), Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Carli
mesh_terms: D000368:Aged; D061345:Early Medical Intervention; D000068817:Epoetin Alfa / Q000008:administration & dosage*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000188:drug therapy*; D016037:Single-Blind Method
chemical_list: D006397:Hematinics; D000068817:Epoetin Alfa
keywords: brain ischemia; cardiopulmonary resuscitation; neuroprotection; reperfusion injury; thrombosis