Carotid Artery DiseasePhase 3NCT07200180
Perioperative Argon Inhalation to Improve Neurocognitive Recovery After Carotid Surgery
A Phase 3 study testing Аrgon-oxygen breathing mixture and Nitrogen-oxygen breathing mixture in people with Carotid Artery Disease and Carotid Artery Stenoses, run by Negovsky Reanimatology Research Institute at 2 sites in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carotid Artery Disease, Carotid Artery Stenoses
- What is being tested?
- Аrgon-oxygen breathing mixture and Nitrogen-oxygen breathing mixture
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 2 sitesRussia
- Study dates
- 22 Sep 2025to 1 Nov 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age > 18 years
- elective carotid artery surgery
- general anesthesia
- written informed consent
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Russia2 sites, 2 recruiting
- Recruiting
GBWZ of Moscow city hospital n.a. S.P. Botkin
Moscow, 125284
Viktoriya Antonova, PhD, +79385003034, vantonova@fnkcrr.ru
Viktoriya Antonova, PhD
- Recruiting
Demikhov Municipal Clinical Hospital 68
Moscow
Viktoriya Antonova, MD, PhD, +79385003034, vantonova@fnkcrr.ru
Dmitriy Makarevich, MD, PhD
About this study
Official title: Perioperative Argon Inhalation to Improve Neurocognitive Recovery After Carotid Surgery (PAIRS Trial)
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.
Read more
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
- Being tested
- Аrgon-oxygen breathing mixture, Nitrogen-oxygen breathing mixture
- Keywords
- Carotid artery disease, Carotid artery stenosis, Carotid artery surgery, Neurocognitive disorders, postoperative delirium, Stroke, Neuroinflammation, Argon, Organ protection
- Medical subject headings
- Carotid Artery Diseases, Carotid Stenosis, Neurocognitive Disorders, Emergence Delirium, Stroke, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Аrgon-oxygen breathing mixtureDrug
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
Nitrogen-oxygen breathing mixtureDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Аrgon-oxygen breathing mixture | Experimental | Perioperative inhalation of an argon-oxygen mixture (70% argon, 30% oxygen) Receives: Drug: Аrgon-oxygen breathing mixture |
| Nitrogen-oxygen breathing mixture | Sham comparator | Perioperative inhalation of an nitrogen-oxygen mixture (70% nitrogen, 30% oxygen) Receives: Drug: Nitrogen-oxygen breathing mixture |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 30 days
Secondary outcomes (11)
Incidence of emergence delirium
Number of patients with positive the confusion assessment method for the intensive care unit as soon as they reach Aldrete score of 9 points
Measured: 30 days
Incidence of postoperative agitation
Richmond agitation-sedation scale more or equal +2 evaluated from the end of volatile anesthetic supply to the moment when a patient reaches Aldrete score of 9 points Richmond agitation-sedation scale: minimum value = -5 (Unarousable - no response to voice or physical stimulation) maximum value = +4 (Combative - overtly combative or violent; immediate danger to staff) Adequate patients have the results of Richmond agitation-sedation score equal 0 (Alert and calm; Spontaneously pays attention to caregiver)
Measured: 30 days
Duration of postoperative delirium
30 days - number of days in which patient had positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method
Measured: until 1 month after surgery
Incidence of cognitive dysfunction
reduction of ≥1 standard deviation in the Montreal Cognitive Assessment (MoCA) total z-score compared to the preoperative assessment
Measured: 30 days
Incidence of overt stroke
Number of overt strokes
Measured: 30 days
Incidence of covert stroke
Number of covert strokes
Measured: 30 days
Length of stay in the intensive care unit
Number of days in intensive care unit
Measured: 30 days
Length of hospitalization
Number of days in hospital
Measured: 30 days
Serum level of S100 beta protein
Serum level of S100 beta protein
Measured: 2 days after surgery
Serum level of neuron-specific enolase
Serum level of neuron-specific enolase
Measured: 2 days after surgery
Serum level of interleukin-6
Serum level of interleukin-6
Measured: 2 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2025
- Study start22 Sep 2025
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carotid Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Negovsky Reanimatology Research Institute
- Sponsor type
- Other government
- Collaborators
- GBWZ of Moscow city hospital n.a. S.P. Botkin
- Responsible party
- Principal investigator, Oleg A. Grebenchikov, Negovsky Reanimatology Research Institute
- Investigators
- Oleg Grebenchikov, MD, PhD, Principal investigator, Negovsky Reanimatology Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07200180
- Sponsor's protocol ID
- PAIRS
- Status last verified
- Jun 2026
- First submitted
- 22 Sep 2025
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Decision of the local ethics committee
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Argon Inhalation to Improve Neurocognitive Recovery After Carotid Surgery (PAIRS Trial)
- ClinicalTrials.gov ID
- NCT07200180
- Acronym / sponsor ID
- PAIRS
- Conditions
- Carotid Artery Disease, Carotid Artery Stenoses
- Keywords
- Carotid artery disease, Carotid artery stenosis, Carotid artery surgery, Neurocognitive disorders, postoperative delirium, Stroke, Neuroinflammation, Argon
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Negovsky Reanimatology Research InstituteOther government
- Collaborators
- GBWZ of Moscow city hospital n.a. S.P. Botkin
- Study start
- 22 Sep 2025 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 30 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Аrgon-oxygen breathing mixture | Experimental | Drug: Аrgon-oxygen breathing mixturePerioperative inhalation of an argon-oxygen mixture (70% argon, 30% oxygen) |
| Nitrogen-oxygen breathing mixture | Sham comparator | Drug: Nitrogen-oxygen breathing mixturePerioperative inhalation of an nitrogen-oxygen mixture (70% nitrogen, 30% oxygen) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- age > 18 years
- elective carotid artery surgery
- general anesthesia
- written informed consent
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Аrgon-oxygen breathing mixturePatients 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 | Аrgon-oxygen breathing mixture |
| Nitrogen-oxygen breathing mixturePatients 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 | Drug | Nitrogen-oxygen breathing mixture |
Primary outcome
Incidence of postoperative delirium
Time frame: 30 days
Number of patients with even one positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method
11 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
- Individual participant dataSharing planned: No. Decision of the local ethics committee
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oleg Grebenchikov, MD, PhD principal investigator
Negovsky Reanimatology Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Аrgon-oxygen breathing mixture and Nitrogen-oxygen breathing mixture in people with Carotid Artery Disease and Carotid Artery Stenoses, run by Negovsky Reanimatology Research Institute at 2 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Oleg Grebenchikov, MD, PhD (+79686494147, oleg.grebenchikov@yandex.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of postoperative delirium (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.