The goal of this follow-on pilot randomized clinical trial is to obtain additional preliminary data to inform a larger, adequately powered phase 2b trial of daridorexant for the prevention of postoperative delirium after heart surgery. Having demonstrated feasibility in a prior study (RSRB #9841), this study aims to estimate the effect of daridorexant on (1) reducing delirium symptom burden and incidence and (2) improving self-reported sleep quality during the postoperative period, and (3) to assess the feasibility of collecting objective sleep data in the postoperative setting.

Participants will: complete a baseline visit; take the study drug, either daridorexant or placebo, each of the first three nights after heart surgery; and be evaluated daily for sleep and delirium during the first three postoperative days. Participants will also have the option of wearing a sleep monitor in the hospital each of the first three nights after surgery.

Inclusion Criteria:

• ≥ 60 yrs;
• having surgical aortic valve surgery or coronary artery bypass graft surgery at Strong Memorial Hospital;
• can provide consent;
• able to speak, read,and write English (as the instruments, including semi-structured interviews, used in this protocol have been validated in English);
• family member or close friend for collateral.

Exclusion Criteria:

• Prior cardiotomy
• Infectious endocarditis
• Emergency surgery
• Delirium at baseline (positive 3D-CAM)
• Auditory or visual impairment that prevents study procedures
• Alcohol or substance misuse (CAGE-AID score ≥ 2)
• Psychotic disorder
• Dementia-level deficits (TICS < 27)
• Use of a prescription sleep aid at least every other night
• Use of a strong CYP3A4 inhibitor (e.g., ceritinib, clarithromycin, cobicistat, idelalisib, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, telithromycin, voriconazole)
• Daridorexant intolerance
• Severe kidney or liver impairment (Child-Pugh ≥7, Cockcroft-Gault <30 mL/min, or on dialysis)
• Narcolepsy
• Suicidal ideation at baseline
• Any condition that, in the PI's opinion, compromises patient safety or data quality
• Additional exclusions for the NLP exploratory aim: history of traumatic brain injury or head concussions with loss of consciousness, use of corticosteroids, or history of major neurological disease or brain surgery

Study drug and placebo will be identical in appearance, labeling, and administration schedule. Randomization and treatment assignment will be managed by the investigational pharmacy. The blind will be maintained for participants, care providers, investigators, and outcome assessors, and will be broken only after data lock or in the event of a medical emergency.