Efficacy and safety of rifampicin for multiple system atrophy: a randomised, double-blind, placebo-controlled trial.
Abstract | BACKGROUND: METHODS: In this randomised, double-blind, placebo-controlled trial we recruited participants aged 30-80 years with possible or probable multiple system atrophy from ten US medical centres. Eligible participants were randomly assigned (1:1) via computer-generated permuted block randomisation to rifampicin 300 mg twice daily or matching placebo (50 mg riboflavin capsules), stratified by subtype (parkinsonian vs cerebellar), with a block size of four. The primary outcome was rate of change (slope analysis) from baseline to 12 months in Unified Multiple System Atrophy Rating Scale (UMSARS) I score, analysed in all participants with at least one post-baseline measurement. This study is registered with ClinicalTrials.gov, number NCT01287221. FINDINGS: Between April 22, 2011, and April 19, 2012, we randomly assigned 100 participants (50 to rifampicin and 50 to placebo). Four participants in the rifampicin group and five in the placebo group withdrew from study prematurely. Results of the preplanned interim analysis (n=15 in each group) of the primary endpoint showed that futility criteria had been met, and the trial was stopped (the mean rate of change [slope analysis] of UMSARS I score was 0.62 points [SD 0.85] per month in the rifampicin group vs 0.47 points [0.48] per month in the placebo group; futility p=0.032; efficacy p=0.76). At the time of study termination, 49 participants in the rifampicin group and 50 in the placebo group had follow-up data and were included in the final analysis. The primary endpoint was 0.5 points (SD 0.7) per month for rifampicin and 0.5 points (0.5) per month for placebo (difference 0.0, 95% CI -0.24 to 0.24; p=0.82). Three (6%) of 50 participants in the rifampicin group and 12 (24%) of 50 in the placebo group had one or more serious adverse events; none was thought to be related to treatment. INTERPRETATION: FUNDING: National Institutes of Health, Mayo Clinic Center for Translational Science Activities, and Mayo Funds.
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Authors | Phillip A Low, David Robertson, Sid Gilman, Horacio Kaufmann, Wolfgang Singer, Italo Biaggioni, Roy Freeman, Susan Perlman, Robert A Hauser, William Cheshire, Stephanie Lessig, Steven Vernino, Jay Mandrekar, William D Dupont, Thomas Chelimsky, Wendy R Galpern |
Journal | The Lancet. Neurology
(Lancet Neurol)
Vol. 13
Issue 3
Pg. 268-75
(Mar 2014)
ISSN: 1474-4465 [Electronic] England |
PMID | 24507091
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Nucleic Acid Synthesis Inhibitors
- Rifampin
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Topics |
- Aged
- Cohort Studies
- Double-Blind Method
- Female
- Follow-Up Studies
- Humans
- Male
- Middle Aged
- Multiple System Atrophy
(diagnosis, drug therapy, epidemiology)
- Nucleic Acid Synthesis Inhibitors
(adverse effects, therapeutic use)
- Rifampin
(adverse effects, therapeutic use)
- Treatment Outcome
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