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

Paganoni S, Hendrix S, Dickson SP, Knowlton N, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson TD, Jackson C, Quinn C, Rothstein JD, Kasarskis EJ, Katz J, Jenkins L, Ladha SS, Miller TM, Scelsa SN, Vu TH, Fournier C, Johnson KM, Swenson A, Goyal N, Pattee GL, Babu S, Chase M, Dagostino D, Hall M, Kittle G, Eydinov M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, Tustison E, Vigneswaran P, Yu H, Cohen J, Klee J, Tanzi R, Gilbert W, Yeramian P, Cudkowicz M

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.

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