TORNA ALL’ELENCO

Efficacy of erythropoietin in amyotrophic lateral sclerosis: A multicentre, randomized, double blind, placebo-controlled, phase III study (EPOS trial) in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

2013
AOU Città della Salute di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (25)Vedi tutti...

Lauria G

Borghero G

Capasso M


et alii...

Abstract

We designed an independent, multicentre, phase III RCT to assess the efficacy of rhEPO 40.000 UI administered i.v. fortnightly as add on treatment to riluzole 100 mg daily over a 12-month period. Inclusion criteria were laboratory-supported, probable, or definite ALS according to El Escorial revised criteria, age between 18 and 75 years, sVC 70% or higher, onset 18 months or less. Patients were randomized 1:1 to rhEPO or placebo based on a permuted-block design stratified to ALSFRS-R score (cut-off 33) and onset (spinal or bulbar). Primary outcomes were survival, tracheotomy or more than 23-h NIV for 14 consecutive days and adverse events causing withdrawal. Secondary outcomes were ALSFRS-R decline, sVC decline, and quality of life (ALSAQ-40). Sample size was estimated on 0.8 power (alpha 0.01, two tails). Analyses were performed by intention-to-treat and per protocol. Twenty-five Italian centers participated in the study. We screened 545 and randomized 208 patients. One patient in rhEPO and seven patients in placebo were lost at enrolment, therefore 103 patients in rhEPO and 97 patients in placebo entered the study. At baseline, arms (rhEPO and placebo, respectively) were balanced as to gender (55 men and 50 men), mean age (59.4 ± 10; 58.6 ± 10), onset (spinal: 73.8%, 74.2%; bulbar: 26.2%, 25.8%), median ALSFRS-R score (40 (21 - 48); 39 (20 - 48)), median sVC (87% (37 - 110), 86% (23 - 114)), median ALSAQ40 (98 (43 - 200); 97 [52 - 161]), riluzole treatment (97%; 95%). At 12-month follow-up, 38 patients dropped-out and 1 was lost in rhEPO arm, whereas 39 patients dropped-out and 2 were lost in placebo arm. Overall rates for survival (9.7% and 7.2%) and tracheotomy or more than 23-h NIV (14.6% and 15.5%) were nonsignificantly different between rhEPO and placebo, even after stratification by onset and ALSFRS-R score at baseline. ALSFRS-R decline did not significantly change in rhEPO compared to placebo ( -2, 95% CI 0 - 4), even after stratification by onset

DOI : 10.3109/21678421.2013.838413/074

Keywords

stratification; follow up; survival; tracheotomy; arm; patient; clinical trial; amyotrophic lateral sclerosis; human; riluzole; placebo; erythropoietin; male; intention to treat analysis; sample size; quality of life; laboratory; gender;