• Sabrina Paganoni, Suzanne Hendrix, Samuel P Dickson, Newman Knowlton, James D Berry, Michael A Elliott, Samuel Maiser, Chafic Karam, James B Caress, Margaret Ayo Owegi, Adam Quick, James Wymer, Stephen A Goutman, Daragh Heitzman, Terry D Heiman-Patterson, Carlayne Jackson, Colin Quinn, Jeffrey D Rothstein, Edward J Kasarskis, Jonathan Katz, Liberty Jenkins, Shafeeq S Ladha, Timothy M Miller, Stephen N Scelsa, Tuan H Vu, Christina Fournier, Kristin M Johnson, Andrea Swenson, Namita Goyal, Gary L Pattee, Suma Babu, Marianne Chase, Derek Dagostino, Meghan Hall, Gale Kittle, Mathew Eydinov, Joseph Ostrow, Lindsay Pothier, Rebecca Randall, Jeremy M Shefner, Alexander V Sherman, Eric Tustison, Prasha Vigneswaran, Hong Yu, Joshua Cohen, Justin Klee, Rudolph Tanzi, Walter Gilbert, Patrick Yeramian, and Merit Cudkowicz.
• Harvard Medical School, Sean M. Healey and AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA spaganoni@mgh.harvard.edu.
• J. Neurol. Neurosurg. Psychiatr. 2022 May 16; 93 (8): 871875871-5.

BackgroundCoformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS).ObjectiveDetermine whether PB/TURSO prolonged tracheostomy/ventilation-free survival and/or reduced first hospitalisation in participants with ALS in the CENTAUR trial.MethodsAdults with El Escorial Definite ALS ≤18 months from symptom onset were randomised to PB/ TURSO or placebo for 6 months. Those completing randomised treatment could enrol in an open-label extension (OLE) phase and receive PB/TURSO for ≤30 months. Times to the following individual or combined key events were compared in the originally randomised treatment groups over a period spanning trial start through July 2020 (longest postrandomisation follow-up, 35 months): death, tracheostomy, permanent assisted ventilation (PAV) and first hospitalisation.ResultsRisk of any key event was 47% lower in those originally randomised to PB/TURSO (n=87) versus placebo (n=48, 71% of whom received delayed-start PB/TURSO in the OLE phase) (HR=0.53; 95% CI 0.35 to 0.81; p=0.003). Risks of death or tracheostomy/PAV (HR=0.51; 95% CI 0.32 to 0.84; p=0.007) and first hospitalisation (HR=0.56; 95% CI 0.34 to 0.95; p=0.03) were also decreased in those originally randomised to PB/TURSO.ConclusionsEarly PB/TURSO prolonged tracheostomy/PAV-free survival and delayed first hospitalisation in ALS.Trial Registration NumberNCT03127514; NCT03488524.© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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