PMID- 25595151 OWN - NLM STAT- MEDLINE DCOM- 20150930 LR - 20181113 IS - 1468-330X (Electronic) IS - 0022-3050 (Print) IS - 0022-3050 (Linking) VI - 86 IP - 8 DP - 2015 Aug TI - Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study. PG - 879-86 LID - 10.1136/jnnp-2014-308996 [doi] AB - OBJECTIVE: To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). METHODS: Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. RESULTS: We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. CONCLUSIONS: RhEPO 40,000 IU fortnightly did not change the course of ALS. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. FAU - Lauria, Giuseppe AU - Lauria G AD - Neuromuscular Disease, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy. FAU - Dalla Bella, Eleonora AU - Dalla Bella E AD - Neuromuscular Disease, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy. FAU - Antonini, Giovanni AU - Antonini G AD - NESMOS Department, Neuromuscular Disease Unit, Sant'Andrea Hospital and University of Rome "Sapienza", Rome, Italy. FAU - Borghero, Giuseppe AU - Borghero G AD - Neurologic Unit, Monserrato University Hospital, Cagliari, Italy. FAU - Capasso, Margherita AU - Capasso M AD - Neurologic Clinic, SS. Annunziata Hospital, Chieti, Italy. FAU - Caponnetto, Claudia AU - Caponnetto C AD - Departments of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Mother and Child Disease, IRCCS University Hospital San Martino IST, Genova, Italy. FAU - Chio, Adriano AU - Chio A AD - Department of Neurosciences, ALS Centre, "Rita Levi Montalcini" Azienda Ospedaliero Universitaria Citta della Salute e della Scienza, Turin, Italy. FAU - Corbo, Massimo AU - Corbo M AD - NEMO Clinical Centre, Milan, Italy Department of Neurorehabilitaton, Casa Cura Policlinico, Milan, Italy. FAU - Eleopra, Roberto AU - Eleopra R AD - Neurology Unit, S. Maria della Misericordia University Hospital, Udine, Italy. FAU - Fazio, Raffaella AU - Fazio R AD - Department of Neurology, IRCCS "San Raffaele" Hospital, Milan, Italy. FAU - Filosto, Massimiliano AU - Filosto M AD - Neurologic Clinic, University of Brescia, Brescia, Italy. FAU - Giannini, Fabio AU - Giannini F AD - Department of Medical and Surgery Sciences and Neurosciences, University of Siena, Siena, Italy. FAU - Granieri, Enrico AU - Granieri E AD - Neurologic Clinic, University of Ferrara, Italy. FAU - La Bella, Vincenzo AU - La Bella V AD - ALS Research Centre, BioNeC, University of Palermo, Palermo, Italy. FAU - Logroscino, Giancarlo AU - Logroscino G AD - Department of Neurology and Psychiatry, University of Bari, Bari, Italy. FAU - Mandrioli, Jessica AU - Mandrioli J AD - Department of Neurosciences, S. Agostino-Estense Hospital, Modena, Italy. FAU - Mazzini, Letizia AU - Mazzini L AD - ALS Centre, Neurologic Clinic, Maggiore della Carita University Hospital, Novara, Italy. FAU - Monsurro, Maria Rosaria AU - Monsurro MR AD - 2nd Neurologic Clinic, 2nd University of Naples, Naples, Italy. FAU - Mora, Gabriele AU - Mora G AD - IRCCS "Salvatore Maugeri" Foundation, Milan, Italy. FAU - Pietrini, Vladimiro AU - Pietrini V AD - Department of Neurosciences, Neurology Unit, University of Parma, Parma, Italy. FAU - Quatrale, Rocco AU - Quatrale R AD - Neurology Unit, dell'Angelo Hospital, Mestre, Italy. FAU - Rizzi, Romana AU - Rizzi R AD - Neurology Unit, Department of Neuro-Motor Diseases, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. FAU - Salvi, Fabrizio AU - Salvi F AD - IRCCS Neurological Sciences Institute, Bologna, Italy. FAU - Siciliano, Gabriele AU - Siciliano G AD - Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy. FAU - Soraru, Gianni AU - Soraru G AD - Department of Neurosciences, University of Padua, Padua, Italy. FAU - Volanti, Paolo AU - Volanti P AD - Intensive Neurorehabilitation Unit, IRCCS "Salvatore Maugeri" Foundation, Mistretta, Italy. FAU - Tramacere, Irene AU - Tramacere I AD - Neuroepidemiology Units, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy. FAU - Filippini, Graziella AU - Filippini G AD - Neuroepidemiology Units, IRCCS Foundation, "Carlo Besta" Neurological Institute, Milan, Italy. CN - EPOS Trial Study Group LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150116 PL - England TA - J Neurol Neurosurg Psychiatry JT - Journal of neurology, neurosurgery, and psychiatry JID - 2985191R RN - 0 (Recombinant Proteins) RN - 11096-26-7 (Erythropoietin) RN - 64FS3BFH5W (Epoetin Alfa) SB - IM MH - Adult MH - Aged MH - Amyotrophic Lateral Sclerosis/*drug therapy/mortality MH - Double-Blind Method MH - Epoetin Alfa MH - Erythropoietin/adverse effects/*therapeutic use MH - Female MH - Humans MH - Male MH - Middle Aged MH - Recombinant Proteins/adverse effects/therapeutic use MH - Treatment Outcome PMC - PMC4515982 OTO - NOTNLM OT - ALS OT - MOTOR NEURON DISEASE FIR - Cazzato, Daniele IR - Cazzato D FIR - Cesnik, Edward IR - Cesnik E FIR - Groppo, Elisabetta IR - Groppo E FIR - Sette, Elisabetta IR - Sette E FIR - Pani, Carla IR - Pani C FIR - Costantino, Emanuela IR - Costantino E FIR - Orlandini, Francesco IR - Orlandini F FIR - Boi, Daniela IR - Boi D FIR - Querin, Giorgia IR - Querin G FIR - D'Ascenzo, Carla IR - D'Ascenzo C FIR - Sagnelli, Anna IR - Sagnelli A FIR - Piccirillo, Giovanni IR - Piccirillo G FIR - Aiello, Marina IR - Aiello M FIR - Chetta, Alfredo IR - Chetta A FIR - Grassi, Andrea IR - Grassi A FIR - Lunetta, Christian IR - Lunetta C FIR - Maestri, Eleonora IR - Maestri E FIR - Padovani, Alessandro IR - Padovani A FIR - Cotelli, Mariasofia IR - Cotelli M FIR - Todeschini, Alice IR - Todeschini A FIR - Morino, Stefania IR - Morino S FIR - Di Pasquale, Antonella IR - Di Pasquale A FIR - Latino, Pamela IR - Latino P FIR - Casali, Stefania IR - Casali S FIR - Battistini, Stefania IR - Battistini S FIR - Pirrelli, Marilena IR - Pirrelli M FIR - Cantello, Roberto IR - Cantello R FIR - Nasuelli, Nicola IR - Nasuelli N FIR - Servo, Serena IR - Servo S FIR - De Gennaro, Riccardo IR - De Gennaro R FIR - Gastaldo, Ernesto IR - Gastaldo E FIR - Georgoulopoulou, Eleni IR - Georgoulopoulou E FIR - Fini, Nicola IR - Fini N FIR - Taiello, Alfonsa C IR - Taiello AC FIR - Colletti, Tiziana IR - Colletti T FIR - Calvo, Andrea IR - Calvo A FIR - Moglia, Cristina IR - Moglia C FIR - Fuda, Giuseppe IR - Fuda G FIR - Marinou, Kalliopi IR - Marinou K FIR - Riva, Nilo IR - Riva N FIR - Cerri, Federica IR - Cerri F FIR - Lopez, Ignazio D IR - Lopez ID FIR - De Cicco, Domenico IR - De Cicco D FIR - Battaglia, Gianluca IR - Battaglia G FIR - Marcello, Norina IR - Marcello N FIR - Rinaldi, Manuela IR - Rinaldi M FIR - Scialo, Carlo IR - Scialo C FIR - Mantero, Vittorio IR - Mantero V FIR - Mascolo, Maria IR - Mascolo M FIR - Carlesi, Cecilia IR - Carlesi C FIR - Caldarazzo Ienco, Elena IR - Caldarazzo Ienco E FIR - Di Muzio, Antonio IR - Di Muzio A FIR - Verriello, Lorenzo IR - Verriello L FIR - D'Amico, Delia IR - D'Amico D FIR - Simone, Isabella L IR - Simone IL FIR - Tortelli, Rosanna IR - Tortelli R FIR - Cortese, Rosa IR - Cortese R FIR - Bartolomei, Ilaria IR - Bartolomei I EDAT- 2015/01/18 06:00 MHDA- 2015/10/01 06:00 PMCR- 2015/07/27 CRDT- 2015/01/18 06:00 PHST- 2014/07/15 00:00 [received] PHST- 2014/09/14 00:00 [accepted] PHST- 2015/01/18 06:00 [entrez] PHST- 2015/01/18 06:00 [pubmed] PHST- 2015/10/01 06:00 [medline] PHST- 2015/07/27 00:00 [pmc-release] AID - jnnp-2014-308996 [pii] AID - 10.1136/jnnp-2014-308996 [doi] PST - ppublish SO - J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):879-86. doi: 10.1136/jnnp-2014-308996. Epub 2015 Jan 16.