Lemborexant for Post-operative Delirium

(PROTEX Trial)

Overseen By Ron Ree, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of British Columbia

Must not be taking: CYP3A inhibitors, Insomnia medications

Disqualifiers: Severe sleep apnea, Narcolepsy, Substance use disorder, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking moderate or strong CYP3A inhibitors or frequently use medications for insomnia more than 4 days a week.

Is lemborexant safe for use in humans?

Lemborexant has been approved for treating insomnia in adults and has been studied for its safety in this context. In a study involving patients with pancreato-biliary disease, lemborexant was found to be safe without increasing the risk of delirium, although mild consciousness changes were observed in one patient. ^{1 2 3 4 5}

How does the drug Lemborexant differ from other treatments for post-operative delirium?

Lemborexant is unique because it is primarily used as a sleep aid, working by blocking orexin receptors in the brain, which are involved in wakefulness. This mechanism is different from other treatments for post-operative delirium, which may not specifically target sleep-wake regulation. ^{6 7 8 9 10}

What is the purpose of this trial?

Post-operative delirium is a common complication following cardiac surgery and is associated with increased 1 year mortality. Currently there are no drug therapies to prevent delirium. Orexin is a neuromodulator thought to play an important role in disordered sleep, one of the instigators of delirium. Lembrorexant is an orexin antagonist, originally approved for sleep, that may also reduce the incidence of delirium. The Investigators propose a pilot study to determine the feasibility of a randomized controlled trial comparing Lembrorexant to placebo in patients following cardiac surgery in reducing the incidence of delirium, and improving sleep.

Eligibility Criteria

This trial is for cardiac surgery patients who may be at risk of post-operative delirium, a condition that can lead to increased mortality. The study aims to include those who could benefit from a drug therapy designed to prevent this complication.

Inclusion Criteria

I was admitted to the hospital after having open heart surgery.

Exclusion Criteria

I often feel very sleepy due to my medication.

Pre-existing delirium (ICDSC score >3 or CAM/CAM-ICU positive) at time of consent

Known allergy or hypersensitivity to study drug

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lemborexant or placebo daily for 7 days post-operatively while in hospital

1 week

Daily in-hospital monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of delirium and sleep quality

7 days

Daily assessments during hospital stay

Post-discharge Follow-up

Participants are monitored for any adverse effects and overall recovery post-hospital discharge

4 weeks

Treatment Details

Interventions

• Lemborexant

Trial Overview The trial is testing Lemborexant, an orexin antagonist originally approved for sleep disorders, against a placebo. It's designed as a pilot study to see if Lemborexant can reduce the incidence of delirium and improve sleep after cardiac surgery.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

The intervention arm will receive the study drug, Lemborexant 5mg, daily for 7 days post-operatively while in hospital.

Group II: Control Placebo Group 1 Intervention

The Control arm will receive the placebo study drug daily for 7 days post-operatively while in hospital.

Lemborexant is already approved in United States, Canada, Japan for the following indications:

Approved in United States as Dayvigo for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults

Approved in Canada as Dayvigo for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance, with or without associated impairment in daily functioning

Approved in Japan as Dayvigo for:

• Treatment of insomnia

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

St. Paul's Hospital, Vancouver (Providence Health Care)

Collaborator

Trials

2

Recruited

1,100+

Providence Health Care, British Columbia

Collaborator

Trials

2

Recruited

12,300+

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Findings from Research

Lemborexant is a dual orexin receptor antagonist approved in December 2019 for treating insomnia in adults, effectively helping with both sleep onset and maintenance.

In addition to its use for insomnia, lemborexant is being studied for treating irregular sleep-wake rhythm disorder in patients with mild to moderate Alzheimer's disease, indicating its potential broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lemborexant: First Approval. Scott, LJ.[2021]

Lemborexant has been shown to significantly reduce the time it takes to fall asleep compared to placebo and is also effective when compared to the active control zolpidem ER, based on two phase 3 trials.

The medication is generally well-tolerated, with fewer severe side effects like cognitive impairment and complex sleep-related behaviors compared to traditional insomnia treatments, making it a suitable option, especially for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder. Waters, K.[2022]

In an open-label extension study involving 267 patients with Lennox-Gastaut syndrome, clobazam significantly reduced average weekly drop seizures by 71.1% at 3 months and 91.6% at 24 months, demonstrating its long-term efficacy.

The most common side effects reported were upper respiratory infections, falls, pneumonia, and somnolence, with the adverse event profile aligning with previous controlled trials, indicating a consistent safety profile for clobazam.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study. Ng, YT., Conry, J., Paolicchi, J., et al.[2022]

References

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

Lemborexant: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Torsades de pointes secondary to intravenous haloperidol after coronary bypass grafting surgery. [2015]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Can Lemborexant for Insomnia Prevent Delirium in High-Risk Patients with Pancreato-Biliary Disease after Endoscopic Procedures under Deep Sedation? [2023]

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

Efficacy of combined use of Suvorexant and Ramelteon in preventing postoperative delirium: a retrospective comparative study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

A clinical view of clobazam. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Acute encephalopathy associated with vigabatrin in a six-month-old girl. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Elevation of brain gamma-aminobutyric acid levels is associated with vigabatrin-associated brain abnormalities on magnetic resonance imaging. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Is reduced ornithine-δ-aminotransferase activity the cause of vigabatrin-associated visual field defects? [2013]