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

Sponsor
Yonsei University
Study ID
NCT07265128
Phase
PHASE4
Status
Not Yet Recruiting

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Conditions

  • Aged
  • Benzodiazepines
  • Cardiopulmonary Bypass
  • Critical Illness
  • Delirium

Eligibility Criteria

Sex
ALL
Age
65 Years - 99 Years
Healthy Volunteers
Not accepted

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.
  • 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.

Study Details

"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."

Key Dates

First listed
Dec 4, 2025
Start date
Dec 31, 2025
Status verified
Nov 2025
Primary completion
Sep 30, 2027
Completion
Sep 30, 2027

Study Design

Enrollment
300 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Active Comparator: Midazolam group
    Patients allocated to receive midazolam during anesthetic induction and rewarming period of cardiopulmonary bypass.
  • Experimental: Remimazolam group
    Patients allocated to receive remimazolam during anesthetic induction and rewarming period of cardiopulmonary bypass.

Primary Outcome Measure

Incidence of postoperative delirium within 4 days after surgery [ Time Frame: From the day of surgery (POD 0) to postoperative day 4 ]

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