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.