Effects of Remimazolam on Postoperative Cognitive Dysfunction and Neuroinflammatory Biomarkers in Patients Undergoing Aortic Arch Surgery

NCT07816068 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: Arch_RMZ vs PPF
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare remimazolam- and propofol-based anesthesia for their effects on postoperative cognitive dysfunction in patients undergoing aortic arch surgery. These procedures involve a substantial risk of cerebral ischemia and reperfusion injury, which may contribute to postoperative cognitive decline. Although experimental studies have suggested potential neuroprotective effects of remimazolam, clinical evidence in patients undergoing high-risk aortic arch surgery remains limited. This prospective, randomized controlled trial will compare the incidence of postoperative cognitive dysfunction between patients receiving remimazolam- or propofol-based anesthesia. In addition, changes in circulating neuroinflammatory and neuronal injury biomarkers will be evaluated to explore the potential mechanisms underlying any neuroprotective effect of remimazolam. The findings may provide clinical evidence to guide anesthetic selection and improve neurological outcomes in patients undergoing aortic arch surgery.

Conditions

Aortic Aneurysm of the Proximal Arch; Aortic Aneurysms Arch; Aortic Arch Disease; Postoperative Delirium (POD); POSTOPERATIVE DELIRIUM AND POSTOPERATIVE COGNITIVE DECLINE; Postoperative Delirium

Keywords

Remimazolam; Propofol; Arch surgery; Arch disease; postoperative delirium; POCD (postoperative clinical decline)

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative cognitive decline

  Postoperative cognitive function will be assessed using the Korean Mini-Mental State Examination (K-MMSE) and the Korean version of the Montreal Cognitive Assessment (MoCA-K). Both assessments will be performed preoperatively and again on postoperative day 7 or before hospital discharge. Postoperative cognitive dysfunction will be defined as a decrease of ≥2 points from the preoperative baseline score in either the K-MMSE or MoCA-K.

  Preoperative baseline to postoperative day 7 or before hospital discharge

Secondary Outcomes (6)

• Change in plasma IL-1β concentration

  Preoperative baseline to 2-4 hours after completion of cardiopulmonary bypass

• Change in plasma TNF-α concentration

  Preoperative baseline to 2-4 hours after completion of cardiopulmonary bypass

• Change in plasma IL-6 concentration

  Preoperative baseline to 24 hours after completion of cardiopulmonary bypass

• Change in plasma IL-10 concentration

  Preoperative baseline to 24 hours after completion of cardiopulmonary bypass

• Change in plasma HMGB1 concentration

  Preoperative baseline through 24 hours after completion of cardiopulmonary bypass

Other Outcomes (1)

• Incidence of postoperative delirium

  Preoperative baseline to postoperative day 7 or before hospital discharge

Study Arms (2)

Remimazolam group

EXPERIMENTAL

Remimazolam Besylate (2mg/mL)

Drug: Remimazolam Besylate

Propofol group

EXPERIMENTAL

Propofol (20mg/mL)

Drug: propofol

Interventions

Remimazolam Besylate DRUG

\- Continuous drug: remimazolam diluted to 2 mg/mL in normal saline - Maintenance: 1-2 mg/kg/h (titrated to BIS 40-60, max 2 mg/kg/h)

Remimazolam group

propofol DRUG

Continuous drug: propofol (undiluted, 20 mg/mL) - Administration: target-controlled infusion (TCI, Marsh model) - Maintenance: 1-1.5 μg/mL (titrated to BIS 40-60)

Propofol group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 19 years or older
• Patients scheduled to undergo total or partial aortic arch replacement for aortic arch disease, with planned circulatory arrest and/or selective cerebral perfusion as a cerebral protection strategy during surgery

You may not qualify if:

• Pre-existing cognitive impairment, defined as Mini-Mental State Examination (MMSE) score \<24
• Acute cerebral hemorrhage or cerebral infarction within the previous 3 months
• History of hypersensitivity to remimazolam or other benzodiazepines
• History of alcohol or substance abuse
• Chronic use of opioids or benzodiazepines
• Severe hepatic impairment (Child-Pugh class C)
• Acute or chronic renal failure requiring dialysis Emergency surgery or acute aortic dissection

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Hana Pharm Co., Ltd.: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

Location

MeSH Terms

Conditions

Aneurysm, Aortic Arch; Emergence Delirium

Interventions

Propofol

Condition Hierarchy (Ancestors)

Aortic Aneurysm, Thoracic; Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Youn Joung Cho, M.D., Ph.D.

CONTACT

82-2-2072-2467; mingming7@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: September 7, 2026
• First Posted: September 11, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: September 17, 2026

Record last verified: 2026-09

Locations

KR (1)