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

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05051397

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke, Acute Thrombectomy Anesthesia, General Cerebrovascular Circulation Carbon Dioxide	Biological: HYPERCAPNIA Biological: NORMOCAPNIA	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 2, 2021

Anticipated Primary Completion Date :

Aug 2, 2023

Anticipated Study Completion Date :

Nov 2, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

ASITN cerebral vascular collaterality score > 2 [Before reperfusion of the occluded vessel]
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.

Secondary Outcome Measures

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

Other Outcome Measures

Pial Vascular Collaterality within the symptomatic ischemic territory at admission [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)
Arterial carbon dioxide tension [At groin puncture and at the end of procedure]
Arterial carbon dioxide tension will be measured at 2 time points.
Cerebral infarction extension [Before thrombectomy and at day 1]
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.
Reperfusion assessed by mTICI [End of procedure]
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.
Procedural delay [End of procedure]
Time frame from angiosuite admission to groin puncture to reperfusion if any
Number of procedural anesthetic and radiological complications [End of procedure]
Procedural Safety outcomes
Number of Death and neurological complications [Day 7]
Safety outcomes

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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