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

NCT07113483 | Recruiting Phase 3 DMC

• 1 other identifier: 35782025
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Cognitive Dysfunction; Orthopedic Procedures; Postoperative Pain Management; Hip Fracture

Keywords

Remimazolam; Midazolam; Regional Anesthesia; Sedation; Cognitive dysfunction; Elderly patients; Trauma

Outcome Measures

Primary Outcomes (1)

• Early postoperative cognitive function assessed by the Confusion Assessment Method (CAM) score

  Cognitive function will be evaluated using the Confusion Assessment Method (CAM) to detect delirium and acute cognitive changes between 24 and 72 hours postoperatively. This tool assesses acute confusion and cognitive impairment to determine the impact of remimazolam vs. midazolam sedation on early postoperative cognition. Unit of Measure: CAM score (binary outcome: presence or absence of delirium) Scale Information: CAM is a diagnostic algorithm (Yes/No criteria). A positive CAM indicates the presence of delirium.

  24 to 72 hours after surgery

Secondary Outcomes (8)

• Intraoperative blood pressure

  Intraoperative period up to 72 hours post-surgery

• Intraoperative heart rate

  Intraoperative period and up to 72 h postoperative

• Vasopressor requirement

  Intraoperative period and up to 72h postoperative

• Time to full orientation after surgery

  Post-anesthesia care unit (PACU) period

• Length of stay in PACU

  Post-anesthesia care unit (PACU) period

Study Arms (4)

Remimazolam with Traumatic Orthopedic Surgery

ACTIVE COMPARATOR

Participants in this arm receive intravenous Remimazolam sedation during regional anesthesia for traumatic orthopedic surgery. Sedation dosing follows the protocol of 5 mg IV over 1 minute with supplemental doses as needed. Propofol infusion may be used as an adjunct.

Drug: REMIMAZOLAM BESYLATE 2.5 Mg in 1 mL INTRAVENOUS INJECTION, POWDER, LYOPHILIZED, for SOLUTION [BYFAVO]

Remimazolam with Non-Traumatic Orthopedic Surgery

ACTIVE COMPARATOR

Participants receive intravenous Remimazolam sedation during regional anesthesia for elective (non-traumatic) orthopedic surgery. Sedation dosing and adjunct propofol use are consistent with the protocol.

Drug: REMIMAZOLAM BESYLATE 2.5 Mg in 1 mL INTRAVENOUS INJECTION, POWDER, LYOPHILIZED, for SOLUTION [BYFAVO]

Midazolam with Traumatic Orthopedic Surgery

ACTIVE COMPARATOR

Participants receive intravenous Midazolam sedation during regional anesthesia for traumatic orthopedic surgery. Dosing is 0.025-0.05 mg/kg IV with supplemental doses if needed. Propofol may be used as adjunct sedation.

Drug: Midazolam

Midazolam with Non-Traumatic Orthopedic Surgery

ACTIVE COMPARATOR

Participants receive intravenous Midazolam sedation during regional anesthesia for elective (non-traumatic) orthopedic surgery. Sedation dosing and propofol adjunct use follow the study protocol.

Drug: Midazolam

Interventions

Midazolam DRUG

Midazolam: A commonly used benzodiazepine for sedation, administered intravenously at 0.025-0.05 mg/kg with supplemental doses as required. Known for effective anxiolysis and sedation but with a longer recovery profile compared to remimazolam.

Also known as: Dormicum, Versed, Midazolam Hydrochloride

Midazolam with Non-Traumatic Orthopedic Surgery; Midazolam with Traumatic Orthopedic Surgery

REMIMAZOLAM BESYLATE 2.5 Mg in 1 mL INTRAVENOUS INJECTION, POWDER, LYOPHILIZED, for SOLUTION [BYFAVO] DRUG

Remimazolam: A novel, ultra-short-acting benzodiazepine used for procedural sedation. Administered intravenously at 5 mg over 1 minute with supplemental dosing as needed. Characterized by rapid onset and quick recovery, with minimal residual sedation.

Also known as: ByfaByfavo, Remimazolam Besylate, Remimazolam

Remimazolam with Non-Traumatic Orthopedic Surgery; Remimazolam with Traumatic Orthopedic Surgery

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Romanian Society for Enteral and Parenteral Nutrition: lead

Study Sites (1)

Clinical Emergency Hospital of Bucharest

Bucharest, Romania

RECRUITING

MeSH Terms

Conditions

Postoperative Cognitive Complications; Hip Fractures; Cognitive Dysfunction; Wounds and Injuries

Interventions

Midazolam; Injections, Intravenous; Powders; remimazolam

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Femoral Fractures; Fractures, Bone; Hip Injuries; Leg Injuries

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Injections; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Liliana Mirea, Associate Professor, MD

  Clinical Emergency Hospital of Bucharest

  PRINCIPAL INVESTIGATOR

• Ana Maria Dumitriu, MD, PhD

  Clinical Emergency Hospital of Bucharest

  STUDY DIRECTOR

Central Study Contacts

Ana Maria Dumitriu, MD, PhD

CONTACT

+40 721 277 447; cotae_ana_maria@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study medications (Remimazolam and Midazolam) will be prepared in identical syringes by a pharmacist not involved in patient care or outcome assessment. Both participants and clinical staff (anesthesiologists, nurses, outcome assessors) will be blinded to treatment allocation. Emergency unblinding is allowed only in the event of severe adverse events.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Study medications (Remimazolam and Midazolam) will be prepared in identical syringes by a pharmacist not involved in patient care or outcome assessment. Both participants and clinical staff (anesthesiologists, nurses, outcome assessors) will be blinded to treatment allocation. Emergency unblinding is allowed only in the event of severe adverse events.

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: August 8, 2025
• Study Start: October 1, 2025
• Primary Completion: January 1, 2026
• Study Completion: February 15, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1)