Postoperative Delirium, Postoperative Insomnia
Conditions
Keywords
Sleep Disturbance, Insomnia, Sleep quality, Suvorexant
Brief summary
The study is a parallel group, double blind, randomized trial. Subjects will be recruited from individuals undergoing elective surgery for orthopedic, abdominal, urologic, gynecologic or spine reasons. Out of 92 subjects, one experimental group of 46 subjects will receive 20 mg Suvorexant beginning the first in-hospital night ("day 0") and continuing for their hospital stay. If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant. For blinding purposes each arm will receive two tablets (two 10 mg tablets or one 10 mg tablet and a placebo). The other control group of 46 subjects will receive placebo (two tablets) and treatment as usual.
Detailed description
It is rare to get a good night's sleep in the hospital. Even routine patient care, including alarm systems, and too much light can lead to sleep disturbance. Failure to achieve enough high-quality sleep has been associated with decreased brain and heart function. The investigators aim to restore usual sleep patterns in hospitalized patients to have a positive influence on patient outcomes and healthcare costs. Suvorexant, the tested drug in our protocol, works on a different brain chemical system than most other sleep drugs, which may account for its ability to restore natural sleep. Suvorexant has been shown to reduce wakefulness during sleep by a reduction in long wake bouts. This reduction has a positive effect on sleep quality. In keeping with Suvorexant's established ability to decrease insomnia in outpatient settings, the investigators will assess its efficacy to improve sleep quality in the hospital environment in patients having surgery who have sleep disturbance. Suvorexant will be administered beginning on the night after surgery and through the hospitalization (it is estimated that stays will be 1-3 days; the investigators will set a maximum of 4 days). If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant. The investigators aim to study the participant's sleep patterns by using a self-wearable electroencephalography (EEG) recording device, the Sleep Profiler, and see patterns such as total sleep time or the stages of sleep such as rapid eye movement (REM), non-REM, etc. Additionally, the investigators hope to determine if concentration, attention, and general cognitive performance are improved as a result of better sleep. Promoting "natural sleep" may improve surgical recovery through the lessening of fatigue and improvements in brain health.
Interventions
DRUGSuvorexant
Suvorexant (Belsomra™) is an orexin receptor antagonist that will be administered as 2 tablets (10mg each) for a starting dose of 20mg. If the dose is not well tolerated (e.g., daytime sleepiness), then the dose may be decreased to 10 mg of Suvorexant.
DRUGPlacebo
The placebo pill will look identical to Suvorexant and will be taken as 2 tablets.
Sponsors
Columbia University
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Raters and subjects will be blinded to treatment. At the study's completion (the last subject completes) the blind will be broken, and data will be turned over for analysis. A study physician will be available on call 24 hours to monitor patient safety issues that may arise during the hospitalization and they will have access to the blind. Furthermore, the Research Pharmacy will maintain the blind.
Intervention model description
This study is a parallel-group, double-blind, randomized trial where 92 subjects will to randomized 1:1 to either receive 20 mg Suvorexant or placebo (two tablets) and treatment as usual.
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Aged 50 years to 90 years old. * Patients getting elective surgeries for orthopedic reasons (e.g., hip or knee replacement), abdominal surgery (e.g., hernia repair, renal cancer), urologic or gynecologic surgery, and spine surgery with a projected inpatient stay of 24 hours or longer. * Patients experiencing insomnia characterized by difficulties with sleep onset, early morning awakening, and/or sleep maintenance three or more times weekly over a three-month period for eligibility.
Exclusion criteria
* Patients who undergo surgery and then are admitted to intensive care. * Coronary artery bypass graft (CABG) or other cardiac surgeries. * Intra-cranial surgery. * Patients taking more than 60 mg of oxycodone or it's equivalent as outpatient * Circadian rhythm disorders. * High score in the Geriatric Depression Scale (GDS) * Moderate to severe dementia (failed t-MoCa) * Severe obstructive sleep apnea (OSA) (Apnea-hypopnea index (AHI)\>30 and/or screen high risk) * Patients receiving Cytochrome P-450 (CYP3) inhibitors or inducers (Inhibitors: clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, and grapefruit. Inducers: phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids). * Vulnerable populations (i.e., children, pregnant women).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total Sleep Time on Day 0 (TST) | Day 0 of in-hospital stay after surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal Trend of TST | Up to Day 4 post-surgery | The longitudinal trend of TST over the four days will be measured using mixed-effect regression. Group, time (day 0-4), and group x time will be included as the fixed effects and a random intercept of subjects to account for within-subject correlation due to repeated measurement. Regression estimates will be reported. |
| Rate of Attrition | Up to Day 4 post-surgery | The rate of attrition over the 4 days will be measured. If any specific patterns are identified, inverse propensity treatment weighting will be performed to adjust the effect of nonrandom dropout. |
| Richards Campbell Self-Report Sleep Scale | Up to Day 4 post-surgery | The Richards Campbell self-report sleep scale will be used to determine the quality of sleep each morning. This five-item, visual analogue scale was designed as an outcome measure for assessing the perception of sleep. The scale evaluates perceptions of depth of sleep, sleep onset latency, number of awakenings, time spent awake, and overall sleep quality. For each item, respondents are given a visual analogue scale and are asked to place a mark on the line indicating where their own experiences fit between two extremes (for example, the degree to which they received a "good night's sleep" or "a bad night's sleep"). Scale lines extend from 0 to 100 mm, and scores are calculated by measuring where responses fall on each line. A total score is obtained by summing each score out of 100 and dividing the total by five. Lower scores indicate a poorer quality of sleep (worse outcome). |
| Number of Participants With Incidence of Delirium | Up to Day 4 post-surgery | The 3-minute diagnostic interview for Confusion Assessment Method (CAM)-defined delirium (3D-CAM) is a brief verbal assessment tool that can be used to test for delirium. For all items, if the subject's answer is 'incorrect', 'yes', 'don't know', 'no response', or 'non-sensical response', then the appropriate (unshaded) column on the right side is checked. Each of the 4 columns designates a CAM feature. If any one box in a column is checked, the feature is considered present. The CAM algorithm is considered positive if the following features are present: Feature 1) Acute onset or fluctuating course and Feature 2) Inattention and either Feature 3) Disorganized thinking or Feature 4) Altered level of consciousness. |
| Sleep Rescue Medication | Enrollment to end of hospital stay | Number of rescue medication divided by the nummber of days stayed. Given the fact that sleep medication is taken only once, this outcome measures the sleep rescue medications per day |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPaul S. Garcia, MD PhD
Columbia University
Participant flow
Recruitment details
The power analysis suggested a total enrollment of 92 subjects. Due to technical difficulties with the Sleep Profiler, the N was increased to maintain adequate statistical power.
Pre-assignment details
All the patients enrolled started the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 7.911 |
| BMI | 26.3 kg/m^2 STANDARD_DEVIATION 5.602 |
| Charlson Comorbidity Score | 2.8 Index STANDARD_DEVIATION 1.591 |
| Insomnia Severity Score (pre-hospitalization) | 16.5 Score STANDARD_DEVIATION 5.559 |
| Race and Ethnicity Not Collected | 0 Participants |
| RASS score | -0.6 Score STANDARD_DEVIATION 0.837 |
| Sex: Female, Male Female | 52 Participants |
| Sex: Female, Male Male | 25 Participants |
| STOP BANG score | 2.69 Score STANDARD_DEVIATION 1.308 |
| Time of end of the surgery After 5pm | 55 Participants |
| Time of end of the surgery Before 5pm | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 50 | 0 / 50 |
| other Total, other adverse events | 1 / 50 | 0 / 50 |
| serious Total, serious adverse events | 1 / 50 | 0 / 50 |
Outcome results
None listed