Suvorexant for Sleep Disorders in ICU Patients

Recruiting at 1 trial location

Overseen By Omid Azimaraghi

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Benzodiazepines, Antidepressants

Disqualifiers: Renal failure, Liver failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

120 Participants Needed

Trial Summary

What is the purpose of this trial?

Investigators will evaluate the efficacy of postoperative oral suvorexant treatment on nighttime wakefulness after persistent sleep onset (WASO) among adult cardiac surgical patients recovering in the cardiac intensive care unit (ICU). The study include patients ≥ 60 years old undergoing coronary artery bypass graft surgery (CABG), with or without valve surgery (aortic or mitral). Patients will receive either oral suvorexant or placebo for 7 nights starting the night after extubation. The primary hypothesis is that suvorexant compared with placebo decreases WASO, as measured by a specialized electroencephalogram (EEG), the SedLine monitor, during the first night in the cardiac ICU. Investigators will also assess total sleep time (TST), time to sleep onset (TSO), and postoperative delirium and delirium-free days.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using chronic benzodiazepines or medications for cognitive decline, you may not be eligible to participate.

What data supports the effectiveness of the drug Suvorexant for sleep disorders in ICU patients?

Suvorexant is approved by the FDA for treating insomnia in adults, helping with both falling asleep and staying asleep, and improving the quality of sleep. It works by blocking orexin receptors, which are involved in wakefulness, thus promoting sleep. ^{1 2 3 4 5}

How is the drug suvorexant unique for treating sleep disorders in ICU patients?

Suvorexant is unique because it works by blocking orexin receptors, which are involved in wakefulness, helping to promote sleep without the deliriogenic effects that other sleep-promoting agents might have. This makes it potentially beneficial for ICU patients who often experience insomnia and delirium. ^{1 2 3 4 6}

Research Team

Balachundhar Subramaniam, M.D.

Principal Investigator

Beths Israel Deaconess Medical Center

Matthias Eikermann, MD, PHD

Principal Investigator

Montefiore Medical Center/Albert Einstein College of Medicine

Eligibility Criteria

This trial is for adults over 60 who are recovering from coronary artery bypass graft surgery in the ICU. They must speak English and not have severe obesity, known pregnancy, significant heart or kidney failure, liver failure, coma, delirium at enrollment time, certain cognitive impairments or psychiatric conditions.

Inclusion Criteria

I am 60 years old or older.

I am scheduled for heart bypass or valve surgery and will be in the ICU afterwards.

Exclusion Criteria

Your heart is not pumping blood well before surgery.

You have certain psychiatric or neurological conditions, such as bipolar disorder, chronic use of benzodiazepines, or recent seizures.

English language limitations (Sleep assessment and delirium assessment tools are only validated in English)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 days

Daily assessments

Preoperative Assessment

Participants complete the Richards-Campbell Sleep Questionnaire (RCSQ) every morning

3 days

Daily assessments

Treatment

Participants receive either suvorexant or placebo for 7 nights starting the night after extubation

7 days

Daily administration

Follow-up

Participants are monitored for postoperative delirium and sleep quality until hospital discharge

Up to 21 days

Daily assessments

Treatment Details

Interventions

• Placebo oral tablet
• Suvorexant

Trial Overview The study tests if suvorexant can improve sleep after surgery by reducing wakefulness during the night. Participants will receive either suvorexant or a placebo for seven nights post-extubation. Sleep quality will be monitored using EEG technology to measure various sleep parameters.

Participant Groups

Group I: Suvorexant Active Control 1 Intervention

Suvorexant 20 mg will be administered p.o. once a day between 9:00pm and 10:00pm for 7 days starting the night after extubation in the ICU.

Group II: Placebo Placebo Group 1 Intervention

Placebo will be administered p.o. once a day between 9:00pm and 10:00pm for 7 days starting the night after extubation in the ICU.

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Suvorexant is a first-in-class medication that works by blocking orexin receptors, which are involved in regulating wakefulness, thereby promoting sleep for individuals with insomnia.

Approved in the US in August 2014, suvorexant is effective for both sleep onset and sleep maintenance insomnia, and is in the process of being registered in other countries, indicating its potential global impact on treating sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant: first global approval. Yang, LP.[2021]

Suvorexant, an orexin receptor antagonist, was found to be generally safe and well tolerated over a 1-year treatment period for patients with primary insomnia, with a notable incidence of somnolence as a common side effect.

In the first month of treatment, suvorexant significantly improved subjective total sleep time by an average of 38.7 minutes and reduced time to sleep onset by 18.0 minutes compared to placebo, indicating its efficacy in enhancing sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Michelson, D., Snyder, E., Paradis, E., et al.[2022]

This trial will assess the efficacy of suvorexant, an FDA-approved sleep aid, in reducing nighttime wakefulness and delirium in 120 older cardiac surgery patients in the ICU.

The study aims to determine if suvorexant can improve sleep quality and reduce the incidence of postoperative delirium, which is important for recovery in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. Azimaraghi, O., Hammer, M., Santer, P., et al.[2021]

Suvorexant (Belsomra®) is a new sleep medication that works by blocking orexin neurons, leading to a rapid onset of sleep, and is effective at a prescribed dose of 10 mg before bedtime.

A highly sensitive urine assay was developed to accurately identify and quantify suvorexant, demonstrating excellent precision and stability, which is crucial for monitoring its use due to potential misuse and interactions with other sedatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). Sullinger, S., Bryand, K., Kerrigan, S.[2017]

In a study involving 12 healthy adults, suvorexant doses of 40 mg and 150 mg did not significantly affect oxygen saturation levels during sleep, indicating it does not impair respiratory function.

Suvorexant was well tolerated with no serious adverse effects reported, suggesting it is safe for use even at doses higher than the maximum recommended dose for treating insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the orexin receptor antagonist suvorexant on respiration during sleep in healthy subjects. Uemura, N., McCrea, J., Sun, H., et al.[2015]

A reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure suvorexant levels in human plasma, demonstrating high precision and accuracy across a wide concentration range (1-1000 ng/mL).

The method has been validated for stability and can support clinical studies for suvorexant, showing that plasma samples remain stable for up to 25 months at -20°C, which is crucial for long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of suvorexant in human plasma using 96-well liquid-liquid extraction and HPLC with tandem mass spectrometric detection. Breidinger, SA., Simpson, RC., Mangin, E., et al.[2019]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Suvorexant: first global approval. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). [2017]

5. England pubmed.ncbi.nlm.nih.gov

Effects of the orexin receptor antagonist suvorexant on respiration during sleep in healthy subjects. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Determination of suvorexant in human plasma using 96-well liquid-liquid extraction and HPLC with tandem mass spectrometric detection. [2019]