Lemborexant to Prevent Post-operative Delirium in Cardiac Surgery Patients

Purpose:

This is a pilot study to determine the feasibility of a larger randomized controlled trial comparing lemborexant to placebo in patients following cardiac surgery. The primary outcome of this feasibility study is to determine the rate of enrolment, adherence and retention of patients. Secondary outcomes will include incidence of postoperative delirium, delirium days, quality of sleep, hospital length of stay, and the safety and adverse side effect profile of Lemborexant.

Hypothesis:

1\) Primary outcome: It is feasible to perform a study of lembrorexant versus placebo in patients after cardiac surgery, as defined by achieving a recruitment rate of at least 70% and adherence rate of 80% to the study protocol and drug administration schedule.

Justification:

Postoperative delirium is a frequent complication after cardiac surgery, with an incidence estimated at 20-52%. It is associated with increased 1 year mortality, longer ICU and hospital length of stay, and declines in functional and cognitive status that may persist for up to one year. Orexin, a neuromodulator regulating sleep and wakefulness, is believed to significantly influence the pathophysiology of delirium through its association with disordered sleep. Thus far, there are no promising therapies in prevention or treatment of post cardiac surgery delirium.

Lemborexant is a novel orexin antagonist that has been approved for treating insomnia, and has shown promising results in some studies in reducing incidence of delirium post-cardiac surgery. However, the generalizability of these studies is limited by small numbers of patients, an exclusively Asian population, variability in clinical settings, use of different clinical delirium assessment tools, and variability in comparator groups. In addition, the safety profile of lembrorexant has not been well established in the cardiac surgery population.

Objectives:

Primary Objective: to determine the rate of enrolment, adherence and retention of patients in a randomized controlled trial comparing Lemborexant to placebo early after cardiac surgery.

Secondary Objective: to compare the incidence of postoperative delirium, quality of sleep as measured by Richard Campbell's Sleep Questionnaire (RCSQ), delirium days, hospital length of stay between Lembrorexant and placebo. To determine the safety and adverse side effect profile of Lemborexant.