Remimazolam vs Midazolam to Reduce Delirium in Adults ≥65 Undergoing CPB Valve Surgery

NCT07265128 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 4-2024-0976
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

"Postoperative delirium is a common and serious complication following cardiac surgery, particularly among older adults who require intensive care. Its incidence is reported to range between 20% and 70% after cardiopulmonary bypass (CPB), and has been associated with prolonged hospitalization, increased medical costs, higher morbidity and mortality, and long-term cognitive decline. Benzodiazepines are frequently used during anesthetic induction in cardiac surgery due to favorable hemodynamic stability, although multiple clinical guidelines have recommended limitation of benzodiazepine exposure because of concerns for delirium. However, robust clinical evidence in cardiac surgery remains limited. Midazolam is currently the most commonly administered benzodiazepine in this setting, though metabolism through hepatic pathways and accumulation of active metabolites may increase the risk of postoperative delirium, especially in older patients and those with organ dysfunction. Remimazolam, a recently approved benzodiazepine, undergoes rapid hydrolysis by plasma esterases and demonstrates predictable pharmacokinetic properties with a markedly shorter context-sensitive half-time compared to midazolam. These pharmacologic features suggest a potentially reduced impact on postoperative delirium risk. Despite this rationale, no randomized controlled trial has evaluated the effect of remimazolam versus midazolam on delirium after CPB-assisted valve surgery. This randomized double-blind controlled trial aims to determine whether remimazolam reduces the incidence of postoperative delirium compared with midazolam in patients aged ≥65 years undergoing valve surgery with CPB. Eligible participants will be randomized in a 1:1 ratio to receive either remimazolam or midazolam for anesthetic induction according to a computer-generated allocation sequence. All other anesthetic management will follow standardized institutional protocols, including depth of anesthesia monitoring. Delirium assessment will be performed three times daily in the intensive care unit using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC) and twice daily on the ward using 3-Minute Diagnostic Interview for CAM (3D-CAM) for four postoperative days. The primary endpoint is the incidence of delirium within four postoperative days. Key secondary outcomes include in-hospital or 30-day mortality and a composite of major postoperative complications. A total of 300 patients (150 per group) will be enrolled to provide 90% statistical power to detect the hypothesized difference in delirium risk between groups, accounting for a 10% dropout rate. Findings from this study are expected to provide high-quality evidence regarding the comparative impact of remimazolam and midazolam on postoperative delirium and may inform anesthetic strategy selection in high-risk cardiac surgical populations."

Conditions

Delirium; Critical Illness; Aged; Cardiopulmonary Bypass; Benzodiazepines

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium within 4 days after surgery

  Occurrence of delirium assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Intensive Care Delirium Screening Checklist (ICDSC), or 3-Minute Diagnostic Interview for CAM (3D-CAM) during the first 4 postoperative days.

  From the day of surgery (POD 0) to postoperative day 4

Study Arms (2)

Midazolam group

ACTIVE COMPARATOR

Patients allocated to receive midazolam during anesthetic induction and rewarming period of cardiopulmonary bypass.

Drug: Midazolam

Remimazolam group

EXPERIMENTAL

Patients allocated to receive remimazolam during anesthetic induction and rewarming period of cardiopulmonary bypass.

Drug: Remimazolam

Interventions

Midazolam DRUG

Participants receive intravenous midazolam 0.05 mg/kg for anesthetic induction and an additional dose (0.065 mg/kg) administered via the cardiopulmonary bypass circuit during rewarming, with all other anesthetic management identical to the experimental arm.

Also known as: Control group

Midazolam group

Remimazolam DRUG

Participants receive intravenous remimazolam 0.2 mg/kg for anesthetic induction and an additional dose (0.26 mg/kg) administered via the cardiopulmonary bypass circuit during rewarming, together with standard cardiac anesthesia care.

Also known as: Byfavo group

Remimazolam group

Eligibility Criteria

• Age: 65 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients aged 65 years or older undergoing heart valve surgery involving cardiopulmonary bypass.

You may not qualify if:

• Emergency surgery, Surgery involving total arch replacement, History of remimazolam anaphylaxis, History of major neurocognitive disorder, Alcohol or substance dependence/abuse, Major depressive disorder, Schizophrenia, Participation in other clinical studies that may affect outcomes, Inability to provide informed consent due to illiteracy, foreign language barrier, or cognitive impairment.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Department of Anaesthesiology and Pain Medicine, Yonsei University College of Medicine

Seoul, 120-752, South Korea

Location

MeSH Terms

Conditions

Delirium; Critical Illness

Interventions

Midazolam; Control Groups; remimazolam

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind design in which participants, care providers, investigators, and outcome assessors are unaware of treatment allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, parallel-group comparison of remimazolam versus midazolam for anesthetic induction in adults over 65yrs undergoing cardiopulmonary bypass valve surgery to evaluate postoperative delirium.

Study Record Dates

• First Submitted: November 23, 2025
• First Posted: December 4, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: December 4, 2025

Record last verified: 2025-11

Locations

KR (1)