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Remimazolam vs. Midazolam for Sedation and Cognitive Outcomes in Orthopedic Surgery

Remimazolam vs. Midazolam for Sedation and Cognitive Outcomes in Orthopedic Surgery

Recruiting
65 years and older
All
Phase 3

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Overview

This study aims to compare two medications, Remimazolam and Midazolam, used for sedation during orthopedic surgeries performed under regional anesthesia. We want to find out which medication provides better sedation during the procedure and which one affects early recovery of brain function after surgery.

Older adults (65 years and above) undergoing surgery for bone injuries or conditions will participate. We will monitor their sedation levels, blood pressure, heart rate, side effects, and how quickly they recover after surgery. We also want to see if either medication causes fewer problems with thinking and memory shortly after surgery.

The study is designed so neither the patients nor the medical staff know which medication is being given, to ensure unbiased results. Participants will be randomly assigned to receive either Remimazolam or Midazolam.

The information gathered will help doctors choose the safest and most effective sedative for older patients undergoing orthopedic surgeries, potentially improving patient comfort and recovery.

Description

  1. Background and Rationale
    • Importance of effective sedation during orthopedic surgery under regional anesthesia
    • Limitations of current sedative agents (Midazolam)
    • Potential advantages of Remimazolam (rapid onset/offset, safety profile)
    • Gaps in knowledge about cognitive outcomes post-procedure in elderly patients 2. Study Objectives
    • Primary: Compare Remimazolam vs. Midazolam effects on sedation and early cognitive recovery
    • Secondary: Hemodynamics, recovery time, adverse events, patient satisfaction 3. Study Design
    • Prospective, randomized, double-blind, 2x2 factorial
    • Four arms: Remimazolam/traumatic, Remimazolam/non-traumatic, Midazolam/traumatic, Midazolam/non-traumatic
    • Single-center study 4. Patient Population and Inclusion/Exclusion Criteria
    • Age, surgery type, cognitive baseline, health status 5. Intervention Details
    • Drug dosing protocols
    • Use of adjunct propofol
    • Blinding and randomization procedures 6. Outcome Measures
    • Primary and secondary endpoints
    • Timing and methods of cognitive assessment (CAM-ICU)
    • Hemodynamic monitoring
    • Recording adverse events 7. Data Collection and Monitoring
    • Schedule of assessments
    • Safety monitoring by DSMB
    • Data confidentiality and storage 8. Statistical Analysis Plan
    • Sample size rationale
    • Statistical methods for primary and secondary outcomes
    • Handling of missing data and confounders 9. Significance and Impact
    • Potential to improve sedation choice in elderly orthopedic patients
    • Benefits for patient safety, recovery quality, and healthcare resources

Sample Detailed Description Text (expand with specifics and references):

Background and Rationale

Orthopedic surgeries in elderly patients often require sedation alongside regional anesthesia to ensure patient comfort and procedural success. Midazolam, a commonly used benzodiazepine, has a well-known sedative profile but is associated with prolonged sedation and cognitive impairment postoperatively in some cases. Remimazolam is a newer ultra-short-acting benzodiazepine with rapid onset and offset, potentially offering better control over sedation depth and faster cognitive recovery.

Currently, limited data exist comparing these agents in the context of orthopedic surgery, especially among older adults who are at higher risk for postoperative cognitive dysfunction. This study aims to fill this gap by rigorously comparing remimazolam and midazolam in a controlled clinical trial setting.

Objectives

The primary objective is to evaluate the impact of remimazolam versus midazolam on periprocedural sedation quality and early postoperative cognitive function, measured by the Confusion Assessment Method (CAM) within 72 hours after surgery.

Secondary objectives include assessment of hemodynamic stability, recovery profiles, incidence of adverse events, difficulty in spinal puncture, and patient satisfaction.

Study Design

This is a prospective, randomized, double-blind, 2x2 factorial trial conducted at the Clinical Emergency Hospital of Bucharest. Patients aged 65 and older undergoing traumatic or non-traumatic orthopedic surgery under regional anesthesia will be randomized into one of four groups.

Interventions

Patients will receive either remimazolam or midazolam following standardized dosing protocols. Propofol will be administered as an adjunct for maintenance sedation, with doses recorded and analyzed.

Outcome Measures

Primary outcomes include CAM scores assessed at multiple postoperative time points. Secondary outcomes include detailed monitoring of blood pressure, heart rate, time to full orientation, PACU stay length, adverse event rates, and subjective patient satisfaction via Likert scales.

Data Collection and Monitoring

Safety and efficacy data will be collected by blinded assessors. An independent Data and Safety Monitoring Board will oversee study progress and patient safety.

Statistical Analysis

Sample size calculations anticipate enrolling 120 participants, ensuring adequate power to detect clinically relevant differences in cognitive outcomes. Data will be analyzed using ANOVA, Kaplan-Meier, and regression models as appropriate.

Significance

This trial aims to provide evidence to guide sedative choice in elderly orthopedic patients, balancing effective sedation with cognitive safety, potentially improving patient outcomes and healthcare delivery.

Eligibility

Inclusion Criteria:

  • Adults aged 65 years or older.
  • Scheduled for traumatic or non-traumatic orthopedic surgery under regional anesthesia.
  • Able to provide informed consent or have a legally authorized representative provide consent.

Exclusion Criteria:

  • Patient refusal to participate.
  • Mini-Cog score less than 3 (indicative of significant cognitive impairment).
  • Severe hepatic or renal failure.
  • Known allergy to benzodiazepines or propofol.
  • History of benzodiazepine dependence.

Study details
    Postoperative Cognitive Dysfunction
    Orthopedic Procedures
    Postoperative Pain Management
    Hip Fracture

NCT07113483

Romanian Society for Enteral and Parenteral Nutrition

15 October 2025

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