A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis.
Détails
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_923C9FD96A89
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis.
Périodique
Plos One
Collaborateur⸱rice⸱s
GERP ALS Study Group
Contributeur⸱rice⸱s
Borisow N., Holm T., Maier A., Meyer T., Budde P., Grehl T., Guettsches AK., Bewersdorff M., Heneka M., Hermann A., Storch A., Frank T., Göricke B., Weishaupt J., Eger K., Hanisch F., Zierz S., Cordes AL., Dengler R., Koerner S., Kollewe K., Petri S., Grosskreutz J., Kunze A., Prell T., Ringer T., Zinke J., Anneser J., Borasio GD., Chahli C., Winkler AS., Boentert M., Stubbe-Draeger B., Young P., Bogdahn U., Franz S., Haringer V., Weidner N., Benecke R., Meister S., Prudlo J., Wittstock M., Dorst J., Hendrich C., Ludolph AC., Sperfeld AD., Weiland U., Neidhardt S., Schrank B., Beck M., Kraft P., Toyka K., Ulzheimer J., Wessig C.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2012
Volume
7
Numéro
6
Pages
e37885
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS).
METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated.
CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.
TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.
METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated.
CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.
TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/02/2013 16:33
Dernière modification de la notice
20/08/2019 15:55
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