Lemborexant Pilot RCT to Assess Feasibility for Preventing Postoperative Delirium After Cardiac Surgery

Postoperative delirium (POD) is a severe and common complication following major surgeries, particularly in elderly patients undergoing cardiac surgery under general anesthesia. It is strongly associated with increased morbidity, prolonged hospital stays, and significantly higher 1-year mortality. Currently, there are no approved pharmacological therapies specifically for preventing POD. The orexin system, a neuromodulatory pathway, plays a critical role in regulating sleep-wake cycles and arousal. Disordered sleep is a known instigator of delirium, suggesting that modulating orexin signaling could offer a novel therapeutic strategy to prevent POD.

This prospective, randomized controlled pilot trial (PROTEX, NCT06648681) plans to enroll an estimated 60 elderly patients undergoing cardiac surgery. Participants will be randomized to receive perioperative lemborexant, an orexin receptor antagonist, or placebo. The primary outcome for this pilot study is feasibility, defined by achieving a recruitment rate of at least 70% and an adherence rate of 80% to the study protocol and drug administration schedule. Secondary outcomes will likely include the incidence and severity of delirium, though specific assessment methods like CAM-ICU or DRS-R98 are not detailed in the abstract.