Clinical Trial: Lemborexant Efficacy and Safety in Liver Cirrhosis-Randomized, Double-Blind, Crossover Clinical Trial.

BACKGROUND AND AIM: No pharmacologic treatment has yet been approved for sleep disturbances in cirrhosis, a high-risk group with substantial prevalence and clinical consequences. Lemborexant has shown efficacy for insomnia, but evidence in cirrhosis is limited.

METHODS

Restoring Sleep in End-Stage Liver Disease (RESTORE) is a prospective, double-blind, placebo-controlled, crossover trial of Lemborexant for patients with cirrhosis in Cipto Mangunkusumo National Referral Hospital. We randomized 82 patients into three arms: Placebo (n = 28), 5 mg Lemborexant (n = 28), and 10 mg Lemborexant (n = 26). Efficacy was assessed via Pittsburgh Sleep Quality Index (PSQI) over a 2-week period. Safety was evaluated using the EncephalApp Stroop Test for hepatic encephalopathy and liver function tests including AST, ALT, and total bilirubin. PSQI was reevaluated post-crossover at week 4 to investigate rebound insomnia.

RESULTS

Lemborexant significantly reduced PSQI at week 2 in both 5 mg (MD: -7.0 ± 3.15; p < 0.001) and 10 mg groups (MD: -8.27 ± 2.68; p < 0.001), indicating better sleep quality. The 5 mg group showed improved Stroop Test reaction time (MD: -23.5 ± 31.3; p < 0.001), suggesting better cognitive function, whereas 10 mg showed a mild but significant increase in reaction time (MD: 16.7 ± 41.3; p = 0.048). Liver function was not different across treatment groups. Post-crossover analysis showed persistent low PSQI scores in active groups who were switched to placebo. Patients who initially received placebo demonstrated improved sleep after receiving Lemborexant.

CONCLUSION

Our study supported the efficacy and safety of Lemborexant, particularly at 5 mg, against sleep problems in cirrhosis. Larger studies with longer follow-up are warranted to strengthen evidence.

CLINICALTRIALS: gov: NCT07480096.