Anesthesia Management in Endovascular Therapy for Ischemic Stroke - 2 (AMETIS 2)

University Hospital, Clermont-Ferrand

Status: Not yet enrolling

Conditions: Thrombectomy; Ischemic Stroke; Anterior Cerebral Circulation; General Anesthesia; Procedural Sedation

Treatments: Procedure: Procedural sedation; Procedure: General Anesthesia

Study type: Interventional

Funder types: Other

Identifiers

NCT07235514

2025-A00169-40 (Other Identifier)

PHRC 2024 CHABANNE

Details and patient eligibility

About

The goal of this clinical trial is to learn what is the best anesthetic management in participants with severe stroke that require a medical intervention called mechanical thrombectomy (MT) done to open the occluded brain vessel.

The main question it aims to answer is:

• Is general anesthesia (GA) better than procedural sedation (PS) for improving functional performance and decrease dependance in daily life 3 months after stroke?

GA (a non-arousable state induced by anesthetic medications that require respiratory assistance) or PS (a state of reduced arousal induced by lesser dose of anesthetic medications that do not require respiratory assistance) are both used for MT. GA enables strict immobility that could facilitate the conduct of MT but lessen blood pressure and blood flow in the brain. PS provides less drop in blood pressure but MT could be more difficult due to possible movement and breathing may be decreased.

Researchers will compare GA with PS to see which one is better for MT success and for the functional consequences of stroke.

Participants will be treated with GA or PS for the intervention of MT and will be followed by researchers during their hospital stay and asked by a telephone interview how is their functional status 3 months after stroke.

Full description

Mechanical thrombectomy (MT) has significantly improved the outcome of anterior circulation large vessel occlusion stroke. The MT procedure could require management by a dedicated anesthesia team to ensure safety and immobility of these frail patients, in order to quickly restore cerebral perfusion and prevent procedural complications. The anesthetic strategy (general anesthesia with tracheal intubation (GA) or procedural sedation with spontaneous ventilation (PS)) can impact the conduct of the procedure and influence the functional outcome. GA ensures immobility and airway control, but can alter blood pressure (BP). PS provides better control of BP but may be associated with respiratory failure and movements that could interfere with intra-arterial navigation.

Three European single-center randomized controlled trials (RCTs) found no difference between GA and PS for their respective primary endpoints. These three trials were pooled in an individual patient data meta-analysis that evaluated functional outcome (modified Rankin Scale mRS) at 3 months as the primary endpoint. 368 patients were included, and GA was associated with a better functional outcome (mean mRS score was 2.8 (95% CI, 2.5-3.1) in the GA group vs. 3.2 (95% CI, 3.0-3.5) in the PS group (difference, 0.43 [95% CI, 0.03-0.83])). The main limitations of this trial were 1) the small sample size (3 small single-center trials), 2/ a possible center effect with over-representation of one trial on the primary endpoint, and 3/ a highly selected population (exclusion of less severe patients (NIHSS<10), stroke presentation > 8 hours and wake up stroke).

Two French multicenter RCTs have recently been published. The GASS trial included 345 patients in four centers with dedicated GA and PS protocols. There was no difference in the primary endpoint, which was functional independence (mRS 0 to 2) at three months (36% for PS vs. 38% for GA (RR, 0.91 [95% CI, 0.69 to 1.19], p = 0.47)). The AMETIS trial included 273 patients in 10 centers with no specified GA or PS protocol. There was no difference in the primary endpoint, which was a composite of functional independence at 3 months and absence of any peri-procedural and medical complications during the first 7 days. The median mRS was 3 (2-5) under GA vs. 3 (2-4) under PS; RR 0.80 [95% CI: 0.53 to 1.22]. GA was strongly associated with the occurrence of arterial hypotension (87.4% vs. 44.9% in the PS group).

However, 1) these multicenter trials had relatively small sample sizes, 2) the time of assessment of the primary outcome measure was highly variable in GASS, and 3) in AMETIS, the BP targets in the GA group were not met and there was heterogeneity in drug management under PS and GA.

These contradictory results reveal a persistent clinical equipoise regarding this important issue.

The AMETIS-2 trial will evaluate almost every patient with anterior circulation large vessel occlusion stroke eligible for MT in different French comprehensive stroke centers.

The trial protocol for PS and GA will use dedicated anesthetic and hemodynamic management protocols.

The primary outcome measure will use an ordinal shift analysis of the mRS score evaluated at 3 months as the primary endpoint.

To extend the effect analysis, functional independence, cognitive and quality of life assessment will be evaluated as secondary endpoints at 3 months.

We therefore hypothesize that, with a dedicated anesthetic protocol and strict hemodynamic control, GA will lead to a better long-term functional outcome after stroke.

Enrollment: 958 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18 years
• Acute ischemic stroke with an occlusion of the intracranial internal carotid artery and/or the proximal middle cerebral artery (M1-M2) with or without association of extracranial occlusion of the cervical internal carotid artery (tandem lesion)
• Eligible for mechanical thrombectomy according to international guidelines
• Informed and signed consent of patient, or if he is unable to consent the consent of patient's relative or emergency procedure in the absence of relative
• National health insurance

Exclusion criteria

• Coma or altered vigilance defined as a score ≥ 2 on the level of consciousness 1A subscale of the NIHSS
• Premorbid disability defined as a mRS > 2
• Posterior circulation stroke
• Associated cerebral hemorrhage
• Stroke complicating another acute illness or postoperative stroke
• Emesis at arrival in angiosuite
• Allergy to anesthetic medication
• Pregnant or breast-feeding women
• Adult under the protection of the law

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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958 participants in 2 patient groups

General anesthesia

Experimental group

Description:

General anesthesia with intubation and mechanical ventilation: ECG, SpO2 and BP. BP will be measured every 2 minutes Hyperglycemia (\>180mg/dL) and hypoglycemia (\<60mg/dL) should be treated (outside of the protocol) Systolic BP: 150 - 180mmHg with Diastolic BP \< 105mmHg Norepinephrine tartrate infusion or Nicardipine on a peripheral intravenous line or on a 3-way venous extender, as necessary EtCO2 35 - 45mmHg SpO2 above 94 %. Glycemia as needed End of procedure: Anesthesia will be immediately stopped and extubation should not be delayed. After the intervention, patients are transferred to the post anesthesia care unit and are then admitted to the stroke unit First 24 hours: SBP\<180mmHg, DBP\<110mmHg and MAP\>65mmHg, SpO2 \> 94 %, temperature \< 38°C, blood glucose 60 - 180mg/dL. Other aspects of monitoring are not modified by the protocol. 24-48h outside of the protocol: non-contrast brain CT or a brain MRI

Treatment:

Procedure: General Anesthesia

Procedural sedation

Experimental group

Description:

Procedural sedation with spontaneous ventilation: ECG, SpO2 and BP. BP will be measured every 2 minutes Hyperglycemia (\>180mg/dL) and hypoglycemia (\<60mg/dL) should be treated (outside of the protocol) Systolic BP: 150 - 180mmHg with Diastolic BP \< 105mmHg Norepinephrine tartrate infusion or Nicardipine on a peripheral intravenous line or on a 3-way venous extender, as necessary Breathing face mask: EtCO2 and oxygen as necessary SpO2 above 94 %. Glycemia as needed End of procedure: Procedural sedation will be immediately stopped. After the intervention, patients are transferred to the post anesthesia care unit and are then admitted to the stroke unit First 24 hours: SBP\<180mmHg, DBP\<110mmHg and MAP\>65mmHg, SpO2 \> 94 %, temperature \< 38°C, blood glucose 60 - 180mg/dL. Other aspects of monitoring are not modified by the protocol. 24-48h outside of the protocol: non-contrast brain CT or a brain MRI

Treatment:

Procedure: Procedural sedation