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Recruiting NCT07200180

Perioperative Argon Inhalation to Improve Neurocognitive Recovery After Carotid Surgery

Phase III Interventional Carotid Artery Disease Carotid Artery Stenoses

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Аrgon-oxygen breathing mixture, Nitrogen-oxygen breathing mixture.
Who it may be relevant to
Registry conditions: Carotid Artery Disease, Carotid Artery Stenoses. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Russia
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Perioperative Argon Inhalation to Improve Neurocognitive Recovery After Carotid Surgery (PAIRS Trial)

Overview

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.

Interventions

  • Drug Аrgon-oxygen breathing mixture
    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
  • Drug Nitrogen-oxygen breathing mixture
    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

Primary outcome measures

  • Incidence of postoperative delirium [Time frame: 30 days]
Secondary outcome measures (11)
  • Incidence of emergence delirium [Time frame: 30 days]
  • Incidence of postoperative agitation [Time frame: 30 days]
  • Duration of postoperative delirium [Time frame: until 1 month after surgery]
  • Incidence of cognitive dysfunction [Time frame: 30 days]
  • Incidence of overt stroke [Time frame: 30 days]
  • Incidence of covert stroke [Time frame: 30 days]
  • Length of stay in the intensive care unit [Time frame: 30 days]
  • Length of hospitalization [Time frame: 30 days]
  • Serum level of S100 beta protein [Time frame: 2 days after surgery]
  • Serum level of neuron-specific enolase [Time frame: 2 days after surgery]
  • Serum level of interleukin-6 [Time frame: 2 days after surgery]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

  • 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Triple blind
Primary purpose
Prevention

Study locations

Russia · 2 centers
  • GBWZ of Moscow city hospital n.a. S.P. Botkin — Moscow
  • Demikhov Municipal Clinical Hospital 68 — Moscow

Identifiers

NCT: NCT07200180 · PAIRS

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗