RT Journal Article
SR Electronic
T1 Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 871
OP 875
DO 10.1136/jnnp-2022-329024
VO 93
IS 8
A1 Sabrina Paganoni
A1 Suzanne Hendrix
A1 Samuel P Dickson
A1 Newman Knowlton
A1 James D Berry
A1 Michael A Elliott
A1 Samuel Maiser
A1 Chafic Karam
A1 James B Caress
A1 Margaret Ayo Owegi
A1 Adam Quick
A1 James Wymer
A1 Stephen A Goutman
A1 Daragh Heitzman
A1 Terry D Heiman-Patterson
A1 Carlayne Jackson
A1 Colin Quinn
A1 Jeffrey D Rothstein
A1 Edward J Kasarskis
A1 Jonathan Katz
A1 Liberty Jenkins
A1 Shafeeq S Ladha
A1 Timothy M Miller
A1 Stephen N Scelsa
A1 Tuan H Vu
A1 Christina Fournier
A1 Kristin M Johnson
A1 Andrea Swenson
A1 Namita Goyal
A1 Gary L Pattee
A1 Suma Babu
A1 Marianne Chase
A1 Derek Dagostino
A1 Meghan Hall
A1 Gale Kittle
A1 Mathew Eydinov
A1 Joseph Ostrow
A1 Lindsay Pothier
A1 Rebecca Randall
A1 Jeremy M Shefner
A1 Alexander V Sherman
A1 Eric Tustison
A1 Prasha Vigneswaran
A1 Hong Yu
A1 Joshua Cohen
A1 Justin Klee
A1 Rudolph Tanzi
A1 Walter Gilbert
A1 Patrick Yeramian
A1 Merit Cudkowicz
YR 2022
UL http://jnnp.bmj.com/content/93/8/871.abstract
AB 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.Deidentified participant data will be made available upon reasonable request. Requests for data sharing can be sent to info@amylyx.com.