Daridorexant to Prevent Post-cardiotomy Delirium

NCT07217912 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY000010860
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Cognitive Decline; Postoperative Delirium

Keywords

delirium; sleep; cognitive decline; Alzheimer disease and related dementias

Outcome Measures

Primary Outcomes (1)

• Delirium incidence and severity

  Participants will be assessed on postoperative days 1-3 using the Delirium Rating Scale, Revised-98 (DRS-R98; range 0-39; higher scores indicate greater severity of delirium symptoms) and 3-minute Diagnostic interview for the Confusion Assessment Method (3D-CAM; 22 dichotomous items used to inform delirium status). Delirium diagnosis is defined per Diagnostic and Manual of Mental Disorders, 5th Edition, Text Revision, and its severity defined as the sum of DRS-R98 score on postoperative days 1-3.

  Postoperative Days 1-3

Secondary Outcomes (1)

• Postoperative sleep quality

  Postoperative Nights 1-3

Study Arms (2)

daridorexant

EXPERIMENTAL

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

Drug: Daridorexant 50 mg

placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Daridorexant 50 mg DRUG

Administered consistent with labeling from the US Food and Drug Administration.

daridorexant

Placebo OTHER

Identical appearing to daridorexant

placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, United States

RECRUITING

MeSH Terms

Conditions

Postoperative Cognitive Complications; Emergence Delirium; Delirium; Cognitive Dysfunction; Alzheimer Disease

Interventions

daridorexant

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Central Study Contacts

Mark Oldham, MD

CONTACT

585-275-3592; mark_oldham@urmc.rochester.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Model Details: Participants will be randomly assigned in a 1:1 ratio, stratified by surgery type (SAVR vs CABG) in blocks of 4, to receive either daridorexant or matching placebo on the first three postoperative nights following heart surgery.

Study Record Dates

• First Submitted: October 14, 2025
• First Posted: October 20, 2025
• Study Start: October 14, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)