Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial. Issue 8 (16th May 2022)

• Record Type: Journal Article
• Authors: Paganoni, Sabrina; Hendrix, Suzanne; Dickson, Samuel P; Knowlton, Newman; Berry, James D; Elliott, Michael A; Maiser, Samuel; Karam, Chafic; Caress, James B; Owegi, Margaret Ayo; Quick, Adam; Wymer, James; Goutman, Stephen A; Heitzman, Daragh; Heiman-Patterson, Terry D; Jackson, Carlayne; Quinn, Colin; Rothstein, Jeffrey D; Kasarskis, Edward J; Katz, Jonathan; Jenkins, Liberty; Ladha, Shafeeq S; Miller, Timothy M; Scelsa, Stephen N; Vu, Tuan H; Fournier, Christina; Johnson, Kristin M; Swenson, Andrea; Goyal, Namita; Pattee, Gary L; Babu, Suma; Chase, Marianne; Dagostino, Derek; Hall, Meghan; Kittle, Gale; Eydinov, Mathew; Ostrow, Joseph; Pothier, Lindsay; Randall, Rebecca; Shefner, Jeremy M; Sherman, Alexander V; Tustison, Eric; Vigneswaran, Prasha; Yu, Hong; Cohen, Joshua; Klee, Justin; Tanzi, Rudolph; Gilbert, Walter; Yeramian, Patrick; Cudkowicz, Merit;
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93:Issue 8(2022)
• Page Start: 871
• Page End: 875
• Publication Date: 2022-05-16
• Subjects: ALS -- RANDOMISED TRIALS -- MOTOR NEURON DISEASE -- NEUROMUSCULAR; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2022-329024
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS). Objective: Determine whether PB/TURSO prolonged tracheostomy/ventilation-free survival and/or reduced first hospitalisation in participants with ALS in the CENTAUR trial. Methods: Adults 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. Results: Risk 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. Conclusions: Early PB/TURSO prolonged tracheostomy/PAV-free survival and delayed first hospitalisation in ALS. Trial registration number: NCT03127514 ; NCT03488524 .