Daridorexant to Prevent Post-cardiotomy Delirium

University of Rochester

Status and phase: Enrolling; Phase 2

Conditions: Postoperative Cognitive Decline; Postoperative Delirium

Treatments: Drug: Daridorexant 50 mg; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07217912

STUDY000010860

Details and patient eligibility

About

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.

Enrollment: 80 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

daridorexant

Experimental group

Description:

Oral daridorexant 50 mg (or 25 mg, if taking a moderate 3A4 inhibitor) each of the first three nights after heart surgery.

Treatment:

Drug: Daridorexant 50 mg

placebo

Placebo Comparator group

Description:

Oral matching placebo each of the first three nights after heart surgery.

Treatment:

Other: Placebo