The Effect of Reversal of Remimazolam Sedation With Flumazenil on Cognitive Function in Patients Undergoing Hip Arthroplasty Under Spinal Anesthesia

This clinical trial aims to establish whether reversing remimazolam sedation with flumazenil can prevent postoperative neurocognitive disorders in patients undergoing total hip replacement surgery. The main questions it aims to answer are:

• Does administering flumazenil after surgery lead to an improvement in cognitive function (measured by the MoCA scale) at 24 hours post-operation compared to a placebo?
• Does this intervention reduce the incidence of postoperative delirium within the first 48 hours? Researchers will compare flumazenil to a placebo (0.9% saline solution) to see if actively reversing sedation leads to better cognitive outcomes and a lower incidence of delirium.

Participants will:

• Undergo a planned total hip replacement surgery under spinal anesthesia.
• Receive sedation with remimazolam during the operation.
• At the end of the surgery, receive an intravenous injection of the study drug (flumazenil) or a placebo.
• Undergo assessments for cognitive function (using the MoCA scale) and delirium (using the 4AT scale) before and at multiple time points after the surgery.
• Complete a questionnaire about their quality of recovery (QoR-15).

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Delirium; Sedation; Remimazolam; Hip Arthroplasty, Total
• Intervention / Treatment: Drug: remimazolam sedation reversal with flumazenil; Drug: placebo

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient qualified for elective, primary, unilateral, total hip replacement.
• Patient assessed on the ASA I-III scale.
• MoCA score obtained during screening ≥ 23 points (to exclude patients with significant pre-existing cognitive impairment).
• Ability to understand information about the study and express informed, written consent to participate.

Exclusion Criteria:

• Known hypersensitivity or allergy to benzodiazepines, flumazenil, local anesthetics
• Contraindications to spinal anesthesia or patient refusal of this anesthesia technique.
• Severe liver dysfunction.
• History of epilepsy or seizures
• Chronic (daily use for > 2 weeks in the last 3 months) use of benzodiazepines or non-benzodiazepine hypnotics (so-called "Z" drugs: zolpidem, zopiclone, zaleplon).
• Alcohol abuse defined as regular consumption of more than: in men: 40 g of pure ethanol at a time; in women: 20 g of pure ethanol at a time, or a history of psychoactive substance dependence.
• Planned revision hip arthroplasty or bilateral surgery.
• Significant neurological or psychiatric diseases that may affect the assessment of cognitive function.
• The need for sedative premedication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flumazenil Group; Patients will receive a single intravenous bolus of 0.5 mg of flumazenil	Drug: remimazolam sedation reversal with flumazenil; Immediately after the skin suture is completed, before leaving the operating room, the patient will receive an intravenous bolus administered over 30 seconds containing the contents of a pre-prepared, coded syringe with flumazenil
Placebo Comparator: Placebo Group; Patients will receive a single intravenous bolus of 0.9% NaCl	Drug: placebo; Immediately after the skin suture is completed, before leaving the operating room, the patient will receive an intravenous bolus administered over 30 seconds containing the contents of a pre-prepared, coded syringe with placebo (0,9% NaCl)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montreal Cognitive Assessment (MoCA) score	The MoCA is a cognitive screening tool. The total score ranges from 0 to 30 points. A higher score indicates better cognitive function.	from baseline (preoperative) to 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of delirium (defined as a score of ≥ 4 on the 4AT scale)		within the first 48 hours after surgery, assessed every 6 hours.
Total duration of delirium episodes in hours		within the first 48 hours after surgery
Preoperative Anxiety Level assessed by Amsterdam Preoperative Anxiety and Information Scale (APAIS)	The Amsterdam Preoperative Anxiety and Information Scale (APAIS) is a questionnaire consisting of 6 items graded on a 5-point Likert scale (ranging from 1 = "not at all" to 5 = "extremely"). The total score ranges from 6 to 30. A higher score indicates higher levels of preoperative anxiety.	baseline (preoperative)
Montreal Cognitive Assessment (MoCA) score	The MoCA is a cognitive screening tool. The total score ranges from 0 to 30 points. A higher score indicates better cognitive function.	at 1 and 6 hours after surgery
Mini Montreal Cognitive Assessment (mini-MoCA) scores (telephone assessment)	mini-MoCA is an abbreviated version of the MoCA used for remote assessment. The total score usually ranges from 0 to 15 points. A higher score indicates better cognitive function.	at 3 and 6 months after surgery
Quality of Recovery-15 (QoR-15) Questionnaire Score	The QoR-15 is a patient-reported outcome measure assessing the quality of recovery after anesthesia and surgery. The total score ranges from 0 to 150. A higher score indicates a better quality of recovery.	at 24 hours after surgery
The duration of hospital stay	measured in days from the date of surgery to the date of hospital discharge.	Assessed up to 30 days post-surgery (or through hospital discharge, whichever occurs first).
Maximum and average pain intensity measured by Numeric Rating Scale (NRS) at the following time points	Pain intensity will be assessed using the Numeric Rating Scale (NRS). The scale ranges from 0 to 10, where 0 indicates "no pain" and 10 indicates "worst pain imaginable".	6, 12, 24, and 48 hours after surgery
Total oxycodone consumption (in mg)		during the first 48 hours after surgery
Mean bispectral index (BIS) during sedation and percentage of time within the optimal range (60-80)		during surgery
Total dose of remimazolam administered (in mg)		during surgery
Dose of vasopressor drugs		during surgery
Need for additional sedative drugs		during surgery

Collaborators and Investigators

• Sponsor: Medical University of Gdansk

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: November 16, 2025
• First Submitted That Met QC Criteria: November 29, 2025
• First Posted (Estimated): December 11, 2025

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: January 1, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Benzodiazepinones; Flumazenil
• Other Study ID Numbers: 429/2025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No