POSTOPERATIVE DELIRIUM, POSTOPERATIVE COGNITIVE DECLINE
Conditions
Keywords
delirium, sleep, cognitive decline, Alzheimer disease and related dementias
Brief summary
The goal of this phase 2 clinical trial is to demonstrate the feasibility of the current study methods and obtain preliminary data for an adequately powered trial of daridorexant with the aim of preventing delirium after heart surgery. The main aims this feasibility trial aims to answer are to demonstrate: (1) the feasibility of study recruitment; (2) the ability deliver study compounds to subjects according to the proposed methods; and (3) completeness of data capture; and (4) recording of potential adverse events. Participants will: (1) complete a baseline visit; (2) take the study drug--either daridorexant or placebo--each of the first 3 nights after heart surgery; and (3) be evaluated for sleep and delirium each of the first three days after heart surgery.
Interventions
Administered consistent with labeling from the US Food and Drug Administration.
OTHERPlacebo
Identical appearing to daridorexant
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants will be randomized to either the daridorexant or placebo arm.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Having surgical aortic valve replacement or coronary artery bypass graft surgery at Strong Memorial Hospital * Can provide informed consent * Able to speak, read, and write English * Family member or close friend available for collateral
Exclusion criteria
* Prior heart surgery * Infectious endocarditis * Emergency surgery * Delirium at baseline * Auditory/visual impairment preventing study procedures * Active alcohol or substance misuse * Psychotic disorder * Dementia-level deficits * Use of a sleep aid before surgery * Use of a strong 3A4 inhibitor * Intolerance to daridorexant * Severe kidney or liver impairment * Narcolepsy * Any condition that, in the opinion of the PI, compromises patient safety or data quality if enrolled in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delirium | First 3 days after surgery | In this feasibility trial, the primary outcome is rate of completion for delirium assessments--not whether patients developed delirium or the scores on delirium assessments. We aimed to evaluate subjects for delirium on each of the first three days after heart surgery using the Delirium Rating Scale, Revised-98, and the 3-minute Diagnostic Interview for the Confusion Assessment Method. Delirium based on DSM-5-TR diagnostic criteria would be diagnosed using the information from these two assessments. Below we report the number of subjects evaluated on each of the postoperative days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Disturbance | First 3 days after surgery | When evaluating subjects on each of the first 3 days after surgery, we ask subjects to rate their sleep on the preceding night using Richards-Campbell Sleep Questionnaire. This scale includes 6 items (sleep-related domains), each scored using a visual analog scale, ranging from 0 to 100. Higher scores indicate better sleep. Given that this is a feasibility study, we report the number of subjects evaluated for sleep on each of the postoperative days. |
Countries
United States
Participant flow
Recruitment details
IRB approval received on October 21, 2024, and the study was concluded on February 16, 2025 (date of last study evaluation).
Participants by arm
| Arm | Count |
|---|---|
| Daridorexant Oral daridorexant 50 mg (or 25 mg, if taking a moderate 3A4 inhibitor) each of the first three nights after heart surgery. | 5 |
| Placebo Oral matching placebo each of the first three nights after heart surgery. | 6 |
| Total | 11 |
Baseline characteristics
| Characteristic | Daridorexant | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 2.9 | 69.6 years STANDARD_DEVIATION 6.3 | 68.8 years STANDARD_DEVIATION 4.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Montreal Cognitive Assessment | 26 units on a scale STANDARD_DEVIATION 2.4 | 25.8 units on a scale STANDARD_DEVIATION 1.8 | 25.9 units on a scale STANDARD_DEVIATION 2.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 11 Participants |
| Region of Enrollment United States | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 5 / 5 | 6 / 6 |
| serious Total, serious adverse events | 0 / 5 | 1 / 6 |
Outcome results
Primary
Delirium
In this feasibility trial, the primary outcome is rate of completion for delirium assessments--not whether patients developed delirium or the scores on delirium assessments. We aimed to evaluate subjects for delirium on each of the first three days after heart surgery using the Delirium Rating Scale, Revised-98, and the 3-minute Diagnostic Interview for the Confusion Assessment Method. Delirium based on DSM-5-TR diagnostic criteria would be diagnosed using the information from these two assessments. Below we report the number of subjects evaluated on each of the postoperative days.
Time frame: First 3 days after surgery
Population: We attempted to perform delirium assessments for subjects on each of the 3 first days after surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Daridorexant | Delirium | Postoperative day 3 | 5 Participants |
| Daridorexant | Delirium | Postoperative day 1 | 5 Participants |
| Daridorexant | Delirium | Postoperative day 2 | 5 Participants |
| Placebo | Delirium | Postoperative day 3 | 5 Participants |
| Placebo | Delirium | Postoperative day 1 | 6 Participants |
| Placebo | Delirium | Postoperative day 2 | 6 Participants |
Secondary
Sleep Disturbance
When evaluating subjects on each of the first 3 days after surgery, we ask subjects to rate their sleep on the preceding night using Richards-Campbell Sleep Questionnaire. This scale includes 6 items (sleep-related domains), each scored using a visual analog scale, ranging from 0 to 100. Higher scores indicate better sleep. Given that this is a feasibility study, we report the number of subjects evaluated for sleep on each of the postoperative days.
Time frame: First 3 days after surgery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Daridorexant | Sleep Disturbance | Postoperative day 3 | 5 Participants |
| Daridorexant | Sleep Disturbance | Postoperative day 2 | 5 Participants |
| Daridorexant | Sleep Disturbance | Postoperative day 1 | 5 Participants |
| Placebo | Sleep Disturbance | Postoperative day 3 | 5 Participants |
| Placebo | Sleep Disturbance | Postoperative day 1 | 6 Participants |
| Placebo | Sleep Disturbance | Postoperative day 2 | 6 Participants |