Perioperative Argon Inhalation to Improve Neurocognitive Recovery After Carotid Surgery

NCT07200180 | Recruiting Phase 3 DMC

• 1 other identifier: PAIRS
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Currently, over 400,000 reconstructive surgeries on carotid arteries are performed annually worldwide, including carotid endarterectomy (CEA) and carotid stenting. These interventions have proven effective in preventing ischemic stroke in patients with hemodynamically significant carotid artery stenoses. However, even following a technically successful procedure, the risk of perioperative ischemic brain injury persists. According to meta-analyses, one in five patients exhibits covert ("silent") strokes after reconstructive interventions, with their frequency being ten times higher than that of clinically manifest events. Such lesions are associated with cognitive decline and an increased risk of dementia. An additional risk factor is the "no-reflow" phenomenon-an impairment of microcirculatory reperfusion that occurs even after the restoration of macrovascular blood flow, thereby limiting the effectiveness of surgical revascularization. Cognitive disorders and postoperative delirium, observed in 15-30% of patients after CEA, adversely affect rehabilitation and long-term prognosis. To date, there are no reliable pharmacological strategies to prevent these complications. In this context, inert gases have attracted significant interest as potential neuroprotective agents. Xenon, despite its proven efficacy, is limited by high cost and challenges in industrial production. Argon, in contrast, is accessible, safe, and technologically straightforward to administer. In preclinical models of stroke and ischemia-reperfusion, argon has demonstrated pronounced anti-apoptotic, anti-inflammatory, and antioxidant effects, mediated through the regulation of TLR2/4-, ERK1/2-, Nrf2-, and NF-κB-dependent signaling pathways. Its ability to suppress microglial activation towards the M1 phenotype and inhibit the NLRP3 inflammasome has been noted, which reduces neuroinflammation and decreases the volume of secondary neuronal damage. Short-term argon inhalation in healthy volunteers has shown a favorable safety profile with no adverse effects on cerebral hemodynamics. Thus, it is highly relevant to clinically test the hypothesis that perioperative inhalation of an argon-containing gas mixture can reduce the incidence of ischemic brain injuries and cognitive impairments in patients undergoing CEA.

Conditions

Carotid Artery Disease; Carotid Artery Stenoses

Keywords

Carotid artery disease; Carotid artery stenosis; Carotid artery surgery; Neurocognitive disorders; postoperative delirium; Stroke; Neuroinflammation; Argon; Organ protection

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium

  Number of patients with even one positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method

  30 days

Secondary Outcomes (11)

• Incidence of emergence delirium

  30 days

• Incidence of postoperative agitation

  30 days

• Duration of postoperative delirium

  until 1 month after surgery

• Incidence of cognitive dysfunction

  30 days

• Incidence of overt stroke

  30 days

Study Arms (2)

Аrgon-oxygen breathing mixture

EXPERIMENTAL

Perioperative inhalation of an argon-oxygen mixture (70% argon, 30% oxygen)

Drug: Аrgon-oxygen breathing mixture

Nitrogen-oxygen breathing mixture

SHAM COMPARATOR

Perioperative inhalation of an nitrogen-oxygen mixture (70% nitrogen, 30% oxygen)

Drug: Nitrogen-oxygen breathing mixture

Interventions

Аrgon-oxygen breathing mixture DRUG

Patients receive a course of inhalations with an argon-oxygen mixture according to the following protocol: 60 minutes on day 1 prior to surgery, 60 minutes one hour before being transferred to the operating room, and 60 minutes on the first postoperative day

Аrgon-oxygen breathing mixture

Nitrogen-oxygen breathing mixture DRUG

Patients receive a course of inhalations with an nitrogen-oxygen mixture according to the following protocol: 60 minutes on day 1 prior to surgery, 60 minutes one hour before being transferred to the operating room, and 60 minutes on the first postoperative day

Nitrogen-oxygen breathing mixture

Eligibility Criteria

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

You may qualify if:

• age \> 18 years
• elective carotid artery surgery
• general anesthesia
• written informed consent

You may not qualify if:

• The presence of any mental disorder according to the International Classification of Diseases 10th Revision which is confirmed by a psychiatrist.
• The presence of any neuromuscular disease according to the International Classification of Diseases 10th Revision
• Heart failure equal 3 or 4 class according to the New York Heart Association Functional Classification
• Pregnant or breast-feeding women
• Inability to undergo a preoperative assessment for any reason
• Previously enrolled in this trial

Sponsors & Collaborators

• Negovsky Reanimatology Research Institute: lead

Study Sites (1)

Demikhov Municipal Clinical Hospital 68

Moscow, Russia

RECRUITING

MeSH Terms

Conditions

Carotid Artery Diseases; Carotid Stenosis; Neurocognitive Disorders; Emergence Delirium; Stroke; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arterial Occlusive Diseases; Mental Disorders; Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Inflammation

Study Officials

• Oleg Grebenchikov, MD, PhD

  Negovsky Reanimatology Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oleg Grebenchikov, MD, PhD

CONTACT

+79686494147; oleg.grebenchikov@yandex.ru

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The head of the laboratory in the Negovsky Reanimatology Research Institute

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: September 30, 2025
• Study Start: September 22, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)