CO2 Modulation in Endovascular Thrombectomy for Acute Ischemic Stroke (COMET-AIS)

Evaluation of the Effect of Moderate and Controlled Hypercapnia on Ischemic Penumbra Vascular Collaterality During General Anesthesia for Anterior Circulation Acute Ischemic Stroke Mechanical Thrombectomy

Acute ischemic stroke due to large vessel occlusion is responsible of cerebral blood flow impairment with a progressive and extensive ischemic process. Cerebral collateral circulation may preserve an ischemic penumbra that could recover providing timely reperfusion of the occluded vessel. Mechanical thrombectomy is the standard of care for anterior circulation large vessel reperfusion. Strategy to promote cerebral blood flow in collateral circulation before reperfusion is scarce and rely mainly on blood pressure maintenance. Carbon dioxide is a potent cerebral vasodilator that could enhance collateral circulation blood flow and cerebral protection before reperfusion. General anesthesia with endotracheal mechanical ventilation could be used for thrombectomy and give the opportunity to modulate and control carbon dioxide tension in the blood. This study will test the effect of moderate hypercapnia on penumbral collateral circulation before reperfusion during mechanical thrombectomy for anterior circulation acute ischemic stroke under general anesthesia.

Study Overview

• Status: Recruiting
• Conditions: Anesthesia, General; Ischemic Stroke, Acute; Cerebrovascular Circulation; Carbon Dioxide; Thrombectomy
• Intervention / Treatment: Biological: HYPERCAPNIA; Biological: NORMOCAPNIA

Detailed Description

Study will compare 2 groups of patients treated for anterior circulation large vessel occlusion stroke thrombectomy under general anesthesia.

After anesthetic evaluation, patients will be randomized to receive moderate hypercapnia targeting an arterial CO2 tension (PaCO2) of 50mmHg or normocapnia targeting a PaCO2 of 40mmHg.

The anesthetic protocol will use:

• Rapid sequence induction for orotracheal intubation with PROPOFOL 2mg/Kg and SUXAMETHONIUM 1mg/Kg
• SUFENTANIL 0,1 µg/Kg and CISATRACURIUM 0,1mg/Kg
• Maintenance with intravenous continuous infusion of PROPOFOL targeting a BISpectral index 40 to 60
• Systolic blood pressure will have to be maintained +/- 10% of preoperative baseline value with limits between 120 and 185mmHg (with NOREPINEPHRINE as needed)
• Mechanical ventilation will use Tidal Volume of 7mL/Kg of ideal body weight, respiratory rate of 15/minute, End expiratory pressure of 5cmH2O. FiO2 will target SpO2 95-98%. Initial End Tidal CO2 (EtCO2) target will be 35mmHg.
• A first arterial blood gas analysis at groin puncture will evaluate CO2 alveolar-arterial gradient in order to obtain the expected PaCO2 in each group with respiratory rate modulation on the ventilator.
• ASITN baseline collaterality score will be evaluated at initial angiography with normocapnia in each group. A second evaluation of ASITN will be done just before deployment of intraarterial revascularisation device in hypercapnia or normocapnia depending on randomisation group.
• Targeted PaCO2 will have to be maintained using EtCO2 surrogate until the end of procedure.
• A second arterial blood gas analysis at the end of procedure will evaluate final PaCO2.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lise Laclautre; Phone Number: +33 4 73 754963; Email: promo_interne_drci@chu-clermontferrand.fr

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • Recruiting
    • CHU
    • Contact: Russell Chabanne, MD MSc; Email: rchabanne@chu-clermontferrand.fr
    • Principal Investigator: Russell Chabanne, MD MSc
    • Sub-Investigator: Anna Ferrier, MD
    • Sub-Investigator: Ricardo Moreno, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Large vessel occlusion anterior circulation stroke (terminal carotid artery and/or middle cerebral artery M1-M2 segment) eligible to mechanical thrombectomy under general anesthesia

Exclusion Criteria :

• Active smoker
• Chronic respiratory failure with ambulatory oxygen supplementation
• Obesity with BMI>40Kg/ m2
• Intubation before the procedure
• Heart failure with intolerance to decubitus
• Severe renal failure
• Suspected elevated intracranial pressure
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HYPERCAPNIA; Under general anesthesia with mechanical ventilation, PaCO2=50mmHg will be targeted	Biological: HYPERCAPNIA; Controlled moderate hypercapnia PaCO2 50mmHg under general anesthesia with mechanical ventilation
Active Comparator: NORMOCAPNIA; Under general anesthesia with mechanical ventilation, PaCO2=40mmHg will be targeted	Biological: NORMOCAPNIA; Controlled normocapnia PaCO2 40mmHg under general anesthesia with mechanical ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ASITN cerebral vascular collaterality score > 2	American Society of Interventional and Therapeutic Neuroradiology (ASITN) cerebral vascular collaterality score ranges from 0 (no collaterals visible to the ischemic site) to 4 (complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion). A score > 2 indicate at least collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase.	Before reperfusion of the occluded vessel

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ASITN cerebral vascular collaterality score	American Society of Interventional and Therapeutic Neuroradiology (ASITN) variation during the procedure	• At initial angiography in normocapnia and • Before reperfusion at randomized arterial CO2 tension level
Volume of cerebral infarction	Evaluated with Magnetic Resonance Imaging in milliliters	24 hours after stroke
Progression of cerebral infarction	Evaluated with Magnetic Resonance Imaging or Computed Tomography in milliliters depending on type of radiological modality for patient selection	24 hours after stroke
Neurological clinical outcome	Ordinal and dichotomized modified rankin scale (mRS) ranging from 0 (no disability) to 6 (death); good outcome will be defined as mRS 0-2.	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pial Vascular Collaterality within the symptomatic ischemic territory at admission	Pial Vascular collaterality evaluated at admission with CT or MRI during patient selection for thrombectomy using the Pial Arterial Filling Score (from 0 indicated no collaterality to 5 indicating excellent collaterality)	At admission
Arterial carbon dioxide tension	Arterial carbon dioxide tension will be measured at 2 time points.	At groin puncture and at the end of procedure
Cerebral infarction extension	The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is an imaging measure of the extent of ischemic stroke. Scores range from 0 to 10, with higher scores indicating a smaller infarct core.	Before thrombectomy and at day 1
Reperfusion assessed by mTICI	The modified Treatment In Cerebral Ischemia (mTICI) reperfusion scale ranging from 0 (no perfusion) to 3 (full perfusion with filling of all distal Branches). Good reperfusion will be defined as a score of 2B-3.	End of procedure
Procedural delay	Time frame from angiosuite admission to groin puncture to reperfusion if any	End of procedure
Number of procedural anesthetic and radiological complications	Procedural Safety outcomes	End of procedure
Number of Death and neurological complications	Safety outcomes	Day 7

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Russell Chabanne, MD MSc, University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Willie CK, Macleod DB, Shaw AD, Smith KJ, Tzeng YC, Eves ND, Ikeda K, Graham J, Lewis NC, Day TA, Ainslie PN. Regional brain blood flow in man during acute changes in arterial blood gases. J Physiol. 2012 Jul 15;590(14):3261-75. doi: 10.1113/jphysiol.2012.228551. Epub 2012 Apr 10.
• Slupe AM, Kirsch JR. Effects of anesthesia on cerebral blood flow, metabolism, and neuroprotection. J Cereb Blood Flow Metab. 2018 Dec;38(12):2192-2208. doi: 10.1177/0271678X18789273. Epub 2018 Jul 16.
• Olsen TS, Larsen B, Herning M, Skriver EB, Lassen NA. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke. Stroke. 1983 May-Jun;14(3):332-41. doi: 10.1161/01.str.14.3.332.
• Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24.
• Schonenberger S, Henden PL, Simonsen CZ, Uhlmann L, Klose C, Pfaff JAR, Yoo AJ, Sorensen LH, Ringleb PA, Wick W, Kieser M, Mohlenbruch MA, Rasmussen M, Rentzos A, Bosel J. Association of General Anesthesia vs Procedural Sedation With Functional Outcome Among Patients With Acute Ischemic Stroke Undergoing Thrombectomy: A Systematic Review and Meta-analysis. JAMA. 2019 Oct 1;322(13):1283-1293. doi: 10.1001/jama.2019.11455.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2022
• Primary Completion (Estimated): July 19, 2026
• Study Completion (Estimated): October 19, 2026

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 21, 2021

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: general anesthesia; mechanical thrombectomy; cerebral blood flow; large vessel occlusion stroke; carbon dioxide tension; cerebral collateral circulation
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: COMET-AIS (AOI 2020 Chabanne); AOI... (Other Grant/Funding Number: CHU Clermont-Ferrand)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No