Lemborexant to Prevent Post-operative Delirium in Cardiac Surgery Patients

NCT06648681 | Not Yet Recruiting Phase 2 DMC

• 3 other identifiers: H24-00546NOL 290159NOL 294580
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Delirium - Postoperative; Cardiac Surgery; Cardiac Surgery Subjects; Orexin Antagonist; Feasibility Studies; Sleep; In-hospital Mortality

Keywords

lemborexant; Postoperative Delirium; sleep medication; ICDSC; CAM; cardiac surgery; sleep aid; open heart surgery; delirium; sleep quality; Richards-Campbell Sleep Questionnaire

Outcome Measures

Primary Outcomes (2)

• Recruitment Feasibility

  Recruitment will be deemed feasible if the investigators are able to achieve a minimum recruitment rate of 2 patients per week, with 80% of eligible patients approached consenting to participate.

  Prior to Surgery, for the duration of the study recruitment period, estimated to be approximately 2 years

• Data Collection Adherence

  Data collection adherence will be defined as 80% completion of delirium screening and sleep scores

  Post-operative day 0 to 7

Secondary Outcomes (7)

• Incidence of Postoperative Delirium

  Post-operative day 0 at baseline (immediately before administration of the drug/placebo) and every 12 hours following drug/placebo administration until end of the 7 day follow-up

• Delirium Days

  Post-operative day 0 to 7

• Adverse side effects

  At the time of study drug initiation (T0) and daily following drug/placebo administration (T1 onwards) until end of the 7 day study follow-up.

• Sleep Quality

  Preoperative baseline (time of recruitment/consent T -1), and daily following drug/placebo administration (T1 onwards) until end of the 7 day follow-up.

• Incidence of Additional Sleep Medications

  Post-operative day 0 to 7

Study Arms (2)

Intervention

EXPERIMENTAL

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

Drug: Lemborexant 5 mg

Control

PLACEBO COMPARATOR

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

Drug: Control (placebo) group

Interventions

Lemborexant 5 mg DRUG

The intervention is the oral administration of a study drug containing lemborexant 5 mg daily between 2000h and 0000h for the first 7 days following extubating/initiation criteria is met or until their hospital discharge or until the first diagnosis of delirium, whichever occurs first. Initiation criteria: I. The participant has been extubated for at least 2 hours II. all other sedative medications have been discontinued for \>1 hour III. the participant has a Richmond Agitation and Sedation Scale (RASS) score of \>-1 or a Pasero Opioid-induced Sedation Scale (POSS) score \<3. If satisfactory sleep is not achieved with the 5 mg dose of the study drug, as defined by a Richards Campbell Sleep Score \<50 within 1 hour, another insomnia medication may be administered on participant request and clinician judgement. If participants develop delirium, the study drug will be discontinued.

Intervention

Control (placebo) group DRUG

The control group will receive an oral placebo tablet daily between 2000h and 0000h for the first 7 days following when initiation criteria is met or until their hospital discharge, whichever occurs first. Initiation criteria: I. The participant has been extubated for at least 2 hours II. all other sedative medications have been discontinued for \>1 hour III. the participant has a Richmond Agitation and Sedation Scale (RASS) score of \>-1 or a Pasero Opioid-induced Sedation Scale (POSS) score \<3. If satisfactory sleep is not achieved with the 5 mg dose of the study drug, as defined by a Richards Campbell Sleep Score \<50 within 1 hour, another insomnia medication may be administered on participant request and clinician judgement. If participants develop delirium, the study drug will be discontinued.

Control

Eligibility Criteria

• Age: 61 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admitted to hospital following open cardiac surgery through midline sternotomy

You may not qualify if:

• ● Known severe obstructive sleep apnea diagnosed by polysomnography or STOPBANG score \> 5
• Periodic limb movement disorder or restless legs syndrome
• Narcolepsy
• Somnolence (Pasero Opioid Sedation Scale (POSS) \>2)
• Current alcohol or substance use disorder as defined by the DSM-V
• Patient already taking moderate or strong CYP3A inhibitors
• Frequent use of medications for insomnia defined as \>4 days per week.
• Liver failure (Child-Pugh score B or C)
• Renal failure (eGFR\<30 ml/min/1.73 m2)
• Pre-existing delirium (ICDSC score \>3 or CAM/CAM-ICU positive) at time of consent
• BMI\>40 kg/m2
• Known allergy or hypersensitivity to study drug
• Inability to communicate in English

Sponsors & Collaborators

• University of British Columbia: lead
• Eisai Inc.: collaborator
• Providence Health Care, British Columbia: collaborator
• St. Paul's Hospital, Vancouver (Providence Health Care): collaborator

Study Sites (1)

St. Paul's Hospital

Vancouver, British Columbia, V6Z1Y6, Canada

Location

MeSH Terms

Conditions

Emergence Delirium; Delirium; Sleep Initiation and Maintenance Disorders

Interventions

lemborexant; Population Groups

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Central Study Contacts

Ron Ree, MD

CONTACT

604-561-8348; ronmree@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Model Details: This is a single centre, randomized, double blinded, placebo-controlled pilot trial, with 1:1 allocation of study drug to placebo.

Study Record Dates

• First Submitted: October 12, 2024
• First Posted: October 18, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: April 23, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)