OBJECTIVES: Assisted ventilation and hospitalization are significant drivers of aggregate annual costs and overall health burden in amyotrophic lateral sclerosis (ALS). An oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (PB&TURSO) slowed functional decline in people living with ALS in the 6-month randomized, placebo-controlled phase of the CENTAUR trial. Here, we report final analyses of ALS progression events in CENTAUR inclusive of the long-term, follow-up open-label extension phase.

METHODS: Time to all-cause death, tracheostomy, permanent assisted ventilation (PAV), and first hospitalization were compared between participants originally randomized to PB&TURSO versus placebo at trial end (longest postrandomization follow-up, 42 months). Vital status was ascertained by prospective monitoring or by the participant-locating service OmniTrace. Other events were recorded prospectively via clinic reports.

RESULTS: A total of 135 participants in the modified intent-to-treat population were included in this analysis (original randomization: PB&TURSO, n=87; placebo, n=48). Over the timeframe of follow-up, risk of death was 38% lower in those originally randomized to PB&TURSO versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.40–0.96; P=.032); median (interquartile range [IQR]) survival durations were 23.5 (14.8–39.3) and 18.7 (11.7–31.3) months, respectively. Risk of death or tracheostomy/PAV was 40% lower in those randomized to PB&TURSO versus placebo (HR, 0.60; 95% CI, 0.39–0.92; P=.020), with median (IQR) tracheostomy/PAV-free survival durations of 23.5 (14.8–33.6) and 17.9 (11.7–31.3) months, respectively. Risk of first hospitalization was 40% lower in those randomized to PB&TURSO versus placebo (HR, 0.60; 95% CI, 0.36–1.00; P=.048); median (IQR) times to first hospitalization were 31.8 (6.9–not reached [NR]) and 14.1 (4.2–NR) months, respectively.

CONCLUSIONS: Long-term risk of death, tracheostomy/PAV, and first hospitalization was reduced among those originally randomized to PB&TURSO versus placebo. Limitations include potential for missing data due to loss to follow-up.