Lemborexant for Post-operative Delirium

(PROTEX Trial)

RR
Overseen ByRon Ree, MD
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Lemborexant, a drug originally used for sleep issues, can reduce delirium (a sudden change in mental state) after heart surgery. Delirium commonly affects those recovering from heart surgeries, impacting recovery and overall health. Participants will receive either Lemborexant or a placebo (a pill resembling the drug but without active ingredients) for seven days post-surgery. The trial seeks individuals who have undergone open-heart surgery but do not have severe sleep apnea, restless legs, or certain other medical conditions. As a Phase 2 trial, this research measures Lemborexant's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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 there any evidence suggesting that Lemborexant is likely to be safe for humans?

A previous study found lemborexant safe for patients with pancreato-biliary disease. Importantly, it did not increase the risk of confusion or disorientation (delirium) in those patients, although some mild side effects were reported. The FDA has already approved lemborexant for treating insomnia, which further supports its safety. This approval indicates it is safe for treating sleep problems. However, its use in preventing confusion after surgery remains under study. The current trial phase focuses on assessing its safety and effectiveness for this new purpose, and more data will help confirm its safety for this specific use.12345

Why do researchers think this study treatment might be promising for delirium?

Lemborexant is unique because it targets the orexin system to manage post-operative delirium, unlike most standard treatments that often focus on managing symptoms with antipsychotics or sedatives. This novel mechanism may help regulate sleep-wake cycles more effectively and with fewer side effects. Researchers are excited about Lemborexant because it has the potential to reduce delirium episodes quickly and improve recovery times, offering a promising alternative to traditional approaches.

What evidence suggests that Lemborexant might be an effective treatment for post-operative delirium?

Research has shown that lemborexant, a medication originally approved for sleep problems, might help reduce the risk of confusion after surgery, known as post-operative delirium. One study found that patients who took lemborexant had a 75% lower risk of developing delirium compared to those who did not take it. Another study showed that lemborexant did not worsen delirium in patients with sleep issues. These findings suggest that lemborexant could help manage delirium by improving sleep, which often gets disrupted after surgery. In this trial, participants in the intervention arm will receive lemborexant to evaluate its effectiveness in preventing delirium after surgery. While more research is needed, these early results are promising for its use in preventing delirium after heart surgery.12467

Are You a Good Fit for This Trial?

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
See 10 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: InterventionExperimental Treatment1 Intervention
Group II: ControlPlacebo Group1 Intervention

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

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Approved in United States as Dayvigo for:
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Approved in Canada as Dayvigo for:
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Approved in Japan as Dayvigo for:

Find a Clinic Near You

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 profile image

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno profile image

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

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

Published Research Related to This Trial

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.
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.
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.
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]

Citations

Lemborexant to Prevent Post-operative Delirium in Cardiac ...Secondary outcomes will include incidence of postoperative delirium, delirium days, quality of sleep, hospital length of stay, and the safety and adverse side ...
Can Lemborexant for Insomnia Prevent Delirium in High- ...Lemborexant may be useful for patients with insomnia, without worsening delirium, although there is no evidence for high-risk patients with pancreato-biliary ...
Efficacy of Ramelteon, Suvorexant, and Lemborexant for...Our objective was to evaluate the preventive efficacy of suvorexant, lemborexant, and ramelteon in reducing delirium prevalence and associated clinical outcomes ...
Evaluation of the delirium preventive effect of dual orexin ...The risk of developing delirium was lower with suvorexant (HR 0.22; 95% CI 0.11–0.41) and lemborexant (HR 0.25; 95% CI 0.08–0.81). Conclusion. DORA is a ...
Lemborexant for Post-operative Delirium · Info for ParticipantsIt's designed as a pilot study to see if Lemborexant can reduce the incidence of delirium and improve sleep after cardiac surgery.
Lemborexant to Prevent Post-operative Delirium in Cardiac ...Secondary outcomes will include incidence of postoperative delirium, delirium days, quality of sleep, hospital length of stay, and the safety ...
Study on the delirium preventive effect of lemborexant in ...From February to August 2021, we retrospectively investigated 53 hospitalized patients at high risk of delirium who received LEM for insomnia. We investigated ...
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