Journal Article

Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial

Scelsa, Stephen N, Shefner, Jeremy M, Chase, Marianne, Gilbert, Walter, Randall, Rebecca, Jackson, Carlayne, Katz, Jonathan, Knowlton, Newman, Fournier, Christina, Vigneswaran, Prasha, Berry, James D, Kasarskis, Edward J, Pothier, Lindsay, Yu, Hong, Maiser, Samuel, Eydinov, Mathew, Sherman, Alexander V, Dickson, Samuel P, Babu, Suma, Rothstein, Jeffrey D, Owegi, Margaret Ayo, Dagostino, Derek, Ladha, Shafeeq S, Heitzman, Daragh, Hall, Meghan, Cohen, Joshua, Swenson, Andrea, Ostrow, Joseph, Karam, Chafic, Quinn, Colin, Tustison, Eric, Cudkowicz, Merit, Jenkins, Liberty, Yeramian, Patrick, Elliott, Michael A, Wymer, James, Vu, Tuan H, Caress, James B, Johnson, Kristin M, Goyal, Namita, Heiman-Patterson, Terry D, Kittle, Gale, Klee, Justin, Pattee, Gary L, Goutman, Stephen A, Paganoni, Sabrina, Miller, Timothy M, Tanzi, Rudolph, Quick, Adam, Hendrix, Suzanne

2022

Overview

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 number NCT03127514; NCT03488524.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: ALS / Amyotrophic lateral sclerosis / Drug dosages / Hospitalization / MOTOR NEURON DISEASE / Motor neurone disease / Neuromuscular / Ostomy / Population / RANDOMISED TRIALS / Survival analysis / Tracheotomy