Efficacy and Safety of Lemborexant for Patients With Cirrhosis and Sleep Problems

Safety and Efficacy of Lemborexant for Patients With Cirrhosis and Sleep Problems: a Randomized Clinical Trial

Sleep disturbance poses significant in patients with liver cirrhosis and is associated with impaired quality of life and worsening clinical status. Current pharmacological options remain limited and often have safety concerns due to altered hepatic metabolism. Lemborexant, a dual orexin receptor antagonist, promotes physiological sleep by inhibiting orexin-mediated wakefulness pathways. This study aims to evaluate the efficacy and safety of lemborexant for improving sleep in patients with liver cirrhosis.

Patients with liver cirrhosis frequently experience sleep-wake disturbances such as insomnia, delayed sleep onset, or fragmented sleep. These disturbances may contribute to neurocognitive dysfunction and precipitate hepatic encephalopathy. However, conventional hypnotics such as benzodiazepines may worsen encephalopathy and are generally avoided.

Lemborexant selectively antagonizes orexin receptors OX1R and OX2R, modulating sleep without profound respiratory suppression or GABAergic effects. This randomized, three-armed, double-blind placebo-controlled trial aims to determine whether lemborexant improves sleep quality in patients with cirrhosis while maintaining acceptable neurocognitive and safety outcomes.

Inclusion Criteria:

• adults aged 18 years or older;
• willingness to participate in the clinical trial as evidenced by written informed consent; documented diagnosis of liver cirrhosis in the medical record, with disease severity assessed using the Child-Pugh score and supported by imaging findings consistent with cirrhosis on FibroScan or ultrasonography;
• presence of sleep disturbance defined by a Pittsburgh Sleep Quality Index (PSQI) score greater than 5;
• patients receiving inpatient or outpatient care at Cipto Mangunkusumo National General Hospital;
• ability to take oral medication;
• willingness of the patient or caregiver to maintain a sleep diary throughout the study period;
• ability of the patient or caregiver to comply with the clinical trial protocol and complete scheduled serial assessments.

Exclusion Criteria:

• advanced liver cirrhosis defined as Child-Pugh class C;
• current use of medications with significant interactions affecting the metabolism of Lemborexant, including itraconazole, clarithromycin, fluconazole, verapamil, tramadol, rifampicin, carbamazepine, bosentan, efavirenz, etravirine, and modafinil;
• ongoing alcohol consumption or intake of grapefruit juice during the study period;
• pregnancy, breastfeeding, or plans to become pregnant during the study;
• presence of significant comorbid conditions such as autoimmune disease,
• stage V chronic kidney disease, HIV/AIDS, or known or suspected hypersensitivity to the investigational drug;
• concurrent participation in another clinical trial at the time of screening.