Pitolisant for residual excessive daytime sleepiness in OSA patients adhering to CPAP: a randomized trial

Author(s): JL Pépin, O Georgiev, R Tiholov et al.

Pitolisant for residual excessive daytime sleepiness in OSA patients adhering to CPAP: a randomized trial - article image

CHEST Published online 26 October, 2020 | https://journal.chestnet.org/article/S0012-3692(20)35105-9/fulltext

Digest author(s): Dries Testelmansv / 8 June, 2021

Excessive daytime sleepiness (EDS) is a hallmark symptom for many patients with obstructive sleep apnea (OSA) and has a major impact on quality of life. CPAP treatment has been shown to reduce EDS in optimally adherent patients, but residual EDS was reported in 6 to 15% of well-managed CPAP-treated patients. This study tested the efficacy and safety of pitolisant, a selective histamine H3-receptor antagonist with wake-promoting effects, given at 5 mg, 10 mg, or 20 mg once daily compared to placebo over 12 weeks for the treatment of residual EDS in individuals undergoing well-managed CPAP therapy for moderate to severe OSA.

This was a phase 3, double-blind, placebo-controlled, parallel-group multicenter trial, conducted in 35 European sleep centers. Randomization was centralized on a 3:1 (three pitolisant for one placebo) basis. Individual titration of the dose (5, 10 or 20 mg) was performed, based on efficacy and tolerability.

Adults with OSA, treated with CPAP for at least 3 months with a mean nightly CPAP use of ≥ 4 h and demonstrating an apnea hypopnea index ≤ 10/h with CPAP, were eligible for inclusion if they had persistence of EDS, defined as an ESS score of ≥ 12. The primary outcome was change in ESS score. Secondary outcomes included changes in sleep latency on the OSleR test, changes in Clinical Global Impression scale and safety and tolerance.

244 participants were included; 183 in the pitolisant group and 61 in the placebo group. There were no significant differences in demographic or clinical characteristics between the treatment groups. A significant difference of -2.6 in change in ESS was found between the two arms in favor of pitolisant. The ratio of increase in mean sleep latency during the OSleR test was 1.4 in the pitolisant group and 1.2 in the placebo group (P = .050) The maximum dose of pitolisant was 20 mg/day for the majority (79.8%) of the participants in the pitolisant group. Treatment-related adverse events did not differ between groups.

These results show that pitolisant improves residual EDS, both in subjective and objective assessments, in OSA patients who are adherent to CPAP. An overall good safety profile of pitolisant was confirmed as no significant safety signal was found, in particular none with regard to cardiovascular parameters. These findings are complementary to the effects of pitolisant on EDS in OSA patients declining or not adhering to CPAP. A limitation of the study is 12-week duration study period. Longer-term studies are needed to assess long-term efficacy and safety.

Respiratory digests
Sleep and breathing disorders