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J Am Coll Cardiol. 2016 Jul 5;68(1):40-9. doi: 10.1016/j.jacc.2016.04.040.

Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial.

Author information

1
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.
2
Medical Intensive Care Unit, Lariboisière Hospital (APHP) and INSERM U942, Paris, France.
3
Paris Descartes University, Paris, France; SAMU 75, Necker Hospital (AP-HP), Paris, France.
4
SAMU 78, Centre Hospitalier de Versailles, Versailles, France.
5
Medical ICU, CHU Dupuytren, Limoges, France.
6
SAMU 87 and CHU Dupuytren, Limoges, France.
7
SAMU 94, Henri Mondor Hospital (APHP), Créteil, France.
8
CHU de Caen, Pôle Réanimations, Anesthésie, SAMU, Caen, Caen, France.
9
SAMU 54, CHU de Nancy, Nancy, France.
10
Réanimation Médicale et de Médecine Hyperbare, CHU d'Angers, Angers, France.
11
Medical ICU, Centre Hospitalier de Versailles, Versailles, France.
12
SAMU 45, Hôpital de La Source, Orléans, France.
13
Medical-Surgical Intensive Care Unit, Hôpital de La Source, Centre Hospitalier Regional d'Orléans, Orléans, France.
14
Medical ICU, CHU de Nancy, Nancy, France.
15
Medical ICU, François Rabelais University, Inserm U1100 and CRICS group, Tours, France.
16
Emergency Department and SAMU 59, Lille University Hospital, Lille, France.
17
Medical ICU, Hôpital Henri Mondor (APHP), Créteil, France.
18
CHU de Caen, Department of Medical Intensive Care, Caen, France.
19
Service de Réanimation Médicale Brabois, CHU de Nancy, Vandœuvres-les-Nancy, France.
20
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.
21
SAMU 75, Necker Hospital (AP-HP), Paris, France.
22
SMUR & Surgical Intensive Care, Lariboisière University Hospital (APHP) and Paris 7 University Denis Diderot, Paris, France.
23
SMUR Pitié-Salpêtrière (APHP), Paris, France.
24
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.
25
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.
26
Clinical Trial Unit, Central Pharmacy, APHP, Paris, France.
27
Biostatistics and Epidemiology Unit, Hôtel-Dieu Hospital (APHP, Paris, France.
28
Paris Descartes University, Paris, France; Biostatistics and Epidemiology Unit, Hôtel-Dieu Hospital (APHP, Paris, France.
29
Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Paris, France.
30
Paris Descartes University, Paris, France; Clinical Research Unit, Paris Centre and Paris Descartes University, Paris, France.
31
Paris Descartes University, Paris, France; Hematology Department, Necker Hospital (APHP), Imagine institute, INSERM U1123 CNRS erl 8654, Labex des Globules Rouges Grex, Paris, France.

Abstract

BACKGROUND:

Preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs.

OBJECTIVES:

The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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).

KEYWORDS:

brain ischemia; cardiopulmonary resuscitation; neuroprotection; reperfusion injury; thrombosis

PMID:
27364049
DOI:
10.1016/j.jacc.2016.04.040
[Indexed for MEDLINE]
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