Remimazolam vs. Propofol: Impact on Postoperative Delirium in Neurosurgical Patients

Postoperative Delirium Clinical Trial

Official title:

Effect of Remimazolam Versus Propofol Anesthesia on Postoperative Delirium in Neurosurgical Patients: A Randomised, Controlled, Noninferiority Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06115031
• Other study ID #: SMC 2023-08-135
• Status: Recruiting
• Phase: N/A
• Start date: January 29, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: Samsung Medical Center
• Contact: jeayoun kim
• Phone: +821039268786
• Email: kimjy0705[@]naver.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigator aimed to evaluate the incidence of postoperative delirium after remimazolam-based total intravenous anestheisa (TIVA) compared to the propofol-based TIVA in patients undergoing neurosurgery.

Description:

Remimazolam, a short-acting benzodiazepine, has recently gained approval for use in the induction and maintanance of general anesthesia. In American Society of Anesthesiologists (ASA) physical status class I and II patients undergoing general anesthesia, the remimazolam-based TIVA has shown comparable efficacy to propofol-based TIVA while demonstrating a superior safety profile. Remimazolam has exhibited a lower incidence of hypotension, reduced vasopressor requirements, and fewer instances of bradycardia compared to the propofol-based TIVA. The use of benzodiazepine has been associated with an increased risk of postoperative delirium, but there is currently no randomized controlled trial investigating the relationship between remimazolam, a new short-acting benzodiazepine, and postoperative delirium. Therefore, the investigators designed this prospective, randomized, double-blinded, active comparator-controlled, non-inferiority trial to investigate the incidence of postoperative delirium after remimazolam-based TIVA compared with propofol-based TIVA in neurosurgery patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 696
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• American society of anesthesia (ASA) class I - III

Exclusion Criteria:

• Severe respiratory, cardiovascular, or hepatic disease (child-pugh C)
• Dependency on psychiatric drugs or alcohol
• Severe sensory impairments that impede communication
• Preoprative delirium
• Hypersensitivity, allergies, or contraindication to the study drugs.

Related Conditions & MeSH terms

• Delirium
• Emergence Delirium
• Postoperative Delirium

Intervention

Drug:
• Remimazolam
General anesthesia will be induced and maintained using continuous infusion of intravenous remimazolam.
• Propofol
General anesthesia will be induced and maintained using target-controlled infusion of intravenous propofol.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Postoperative nausea and vomiting (PONV)	PONV substudy are pre-planned non-inferioirty substudy for this main trial. In addition to the data collected as part of the main trial, patients enrolled into the PONV substudy were assessed the frequency and severity of nausea and vomiting, and frequency of antiemetic administration using validated questinnaire.	within 3 days after surgery
Other	Subgroup analysis of delirium incidence assessed by CAM-ICU or 3D-CAM	Subgroup analysis according to the surgery type, patients' age, and preoperative cognitive function and frailty	assessed up to postoperative day 5 or patient discharge, whichever came first
Other	Electroencephalography (EEG)	EEG substudy are pre-planned. The association between the development of postoperative delirium, pre&postoperative cognitive function, severe postoperaitve pain and spectral power of alpha, beta, delta, and theta band. Phase-amplitude coupling of each bands	Intraoperative period
Primary	Postoperative delirium	The occurence of postoperative delirium will be assessed twice a day using confusion assessment method for the intensive care unit (CAM-ICU) and 3-minute diagnostic assessment for CAM-defined delirium (3D-CAM).	assessed up to postoperative day 5 or patient discharge, whichever came first
Secondary	Onset of postoperative delirium	The time of initial diagnosis of postoperative delirium	From the end of surgery until the date of first diagnosis of delirium or discharge, whichever came first, assessed up to postoperative day 5
Secondary	Delirium subtypes	Hypoactive/hyperactive/mixed	assessed twice a day up to postoperative day 5 or patient discharge, whichever came first
Secondary	Severity of postoperative delirium	Severity of postoperative delirium will be assessed twice a day using DRS-R-98 (delirium rating scale-revised-98)	assessed twice a day up to postoperative day 5 or patient discharge, whichever came first
Secondary	Duration of postoperative delirium	Duration of postoperative delirium will be assessed twice a day	assessed twice a day up to postoperative day 5 or patient discharge, whichever came first
Secondary	Subsyndromal delirium	Presence of any CAM features with absence of full syndromal delirium	assessed twice a day up to postoperative day 5 or patient discharge, whichever came first
Secondary	Delirium symptoms	Subsyndromal delirium plus syndromal delirium	assessed twice a day up to postoperative day 5 or patient discharge, whichever came first
Secondary	The proportion of valid delirium assessment	The percentage of valid delirium assessments (per patient) that did not involve coma or stupor out of a total of 14 delirium assessments.	assessed twice a day up to postoperative day 5 or patient discharge, whichever came first
Secondary	Intensive care unit (ICU) admission with endotracheal intubation after surgery	Percentage of the patients who were not extubated in the OR and transferred to the ICU	assessed up to postoperative day 5 or patient discharge, whichever came first
Secondary	Emergence agitation	defined as Richmond Agitation-Sedation Scale =+1	within 30 min after extubation
Secondary	Postoperative pain score	Pain level will be assessed using numeric rating score (NRS)	assessed once a day up to postoperative day 5 or patient discharge, whichever came first
Secondary	Opioid consumption	The amount of opioid consumption will be coverted to parenteral morphine equivalent dose (MED).	assessed once a day up to postoperative day 5 or patient discharge, whichever came first
Secondary	Intraoperative awareness	Intraoperative awareness will be assess using Modified brice questionnaire.	at postoperative day 0
Secondary	Undesirable patient movement	Undesirable movement of patient during surgery	Intraoperative period
Secondary	Potential adverse event	hypotension, hypertension, bradycardia, tachycardia, desaturation, teeth injury, laryngeal spasm, allergic reaction, other arrhtymia, cardiac events, pruritis, nausea, vomiting etc	From the beginning of anesthesia until 24 hours after surgery
Secondary	Perioperative serious adverse events	Serious adverse events are adverse events that result in hospitalization or prolong hospitalization, cause persistent or significant disability, are life-threatening, or result in death.	rom date of randomization until 24 hour after surgery
Secondary	Postoperative complication	assessed by Clavien-Dindo classification Data are presented as the proportion of patients with 1 or more events (edema, vasospasm, rebleeding, seizures, and/or ischemia, etc..)	Until 30 day after surgery
Secondary	Length of stay in ICU after surgery	days	from the day of surgery to the time of patient discharge from ICU, assessed up to 3 months after surgery
Secondary	Length of stay in hospital after surgery	days	from the day of surgery to the time of patient discharge, assessed up to 3 months after surgery
Secondary	Acute kidney injury (AKI) after surgery	AKI assessed by KDIGO criteria	within 1 week after surgery
Secondary	Myocardial injury after non-cardiac surgery (MINS)	MINS assessed by high-sensitive TnT	within 1-month after surgery
Secondary	Fall	the incidence of postoperative fall-down and associated injury (presence of fracture)	3-month after surgery
Secondary	Postoperative cognitive dysfunction	assessed by T-MOCA (Montreal Cognitive Assessment) using telephone interview	3-month after surgery
Secondary	Functional status	assessed using bartel activity of daily living (ADL) index	3-month after surgery
Secondary	Death	All-cause mortality	during hospitalization (up to day 30), within 1 year after surgery (3, 6, and 12-month after surgery)