AMETIS: Anesthesia Management in Endovascular Therapy for Ischemic Stroke

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Completed

CT.gov ID

NCT03229148

Collaborator

Direction Générale de l'Offre de Soins (Other)

332

Enrollment

Location

Arms

Actual Duration (Months)

9.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objective of the study: to assess whether pharmacological sedation or general anesthesia for treatment of anterior circulation ischemic stroke with endovascular mechanical thrombectomy is associated with difference in morbidity (neurological outcome and peri-procedural complications).

Condition or Disease	Intervention/Treatment	Phase
Stroke Thrombectomy Anesthesia Conscious Sedation	Procedure: General anaesthesia Procedure: Conscious Sedation	N/A

Detailed Description

Since 2015, the management of anterior acute ischemic stroke (AIS) involves endovascular treatment with mechanical thrombectomy (MT). This urgent, difficult and uncomfortable procedure in frail patients requires multidisciplinary care ideally involving neurologists, interventional neuroradiologists and anesthesiologists.

Two anesthetic strategies are currently used: pharmacologic sedation in spontaneous ventilation or general anesthesia with tracheal intubation. General anesthesia provides strict immobility, protects the airway and avoids emergency intubation in case of severe procedural complication (notably vomiting and aspiration). Sedation is a frequently used alternative because of (1) a rapid execution which could reduce delay to reperfusion, (2) a lower risk of blood pressure drop that may compromise cerebral blood flow in the penumbra area, (3) the theoretical capacity to assess neurological status during the procedure and (4) the supposed risk of complications associated with mechanical ventilation and intravenous anesthestics on brain metabolism. Nevertheless, sedation exposes to dramatic complications in case of patient agitation and movements.

The choice of the ideal anesthesic management is still lacking. Old retrospective studies seemed to favor sedation with worst neurological outcome associated with general anesthesia. Nevertheless, these datas suffered methodological issues with selection bias: more severe patients based on NIHSS score were rather treated with general anesthesia and blood pressure was not controlled. Recent studies that demonstrated the benefit of MT did not include a specific anesthetic protocol and none of the studies currently available included a blood pressure management protocol that appears to be an essential component of cerebral perfusion. A subgroup analysis of the MR Clean study, including patients with an identical initial NIHSS score, did not find benefit from MT in patients with general anesthesia compared to those receiving sedation. Finally, authors concluded that performing a MT under general anesthesia would significantly lengthen the reperfusion delay and nullify the benefit of MT.

The prospective, randomized, single-center SIESTA trial, conducted in 150 patients with an anterior circulation AIS, found no difference in the early neurological improvement (primary endpoint), assessed on the change in NIHSS score between admission and the 24th hour, between the conscious sedation group and the general anesthesia group. There were a tendency for a better 3-month neurological outcome in the general anesthesia group (37% vs 18% of patients with a Modified Rankin score of 0-2 in the general anesthesia and conscious sedation groups respectively), but it was not possible to conclude due to a lack of statistical power.

Due to the increasing number of patients eligible for endovascular MT and the potential implication of these two anesthetic management on the functional outcome, a study comparing general anesthesia and sedation during a MT seems essential as specified in the recent updated American Stroke Association guidelines.

The objective of this study is to assess whether sedation or general anesthesia during endovascular treatment with mechanical thrombectomy is associated with a difference in morbidity (neurological outcome and peri-procedural complications), in anterior circulation AIS.

Study Design

Study Type:

Interventional

Actual Enrollment :

332 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicentic, prospective, open, in parallel groups, stratified and randomised study.Multicentic, prospective, open, in parallel groups, stratified and randomised study.

Masking:

Single (Outcomes Assessor)

Masking Description:

It is an open label trial because it is not possible to maintain the anesthesiologist and patient blinded during the procedure. However, all subsequent evaluations will be conducted by clinical research staff blinded to the randomization group.

Primary Purpose:

Treatment

Official Title:

Anesthesia Management in Endovascular Therapy for Ischemic Stroke: A Multicenter Randomised Study

Actual Study Start Date :

Aug 31, 2017

Actual Primary Completion Date :

May 13, 2020

Actual Study Completion Date :

Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: General anaesthesia In the general anesthesia group, rapid sequence induction is used. Conduction of general anesthesia and drugs used are left to the expertise of each investigating center. Systolic blood pressure has to be maintained between 140 and 180 mmHg with an intravenous norepinephrine infusion if necessary, tele-expiratory carbon dioxyde concentration (EtCO2) has to be maintained between 30 and 35 mmHg and SpO2 has to be maintained between 94 and 98 %.	Procedure: General anaesthesia Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery
Active Comparator: Conscious Sedation In the conscious sedation group, drugs choice as well as pharmacological modulation will be left to the expertise of each investigating center. A sedation level between 0 and -3 with spontaneous breathing will be targeted, using the Richmond Agitation Sedation Scale (RASS) score validated in French. The lightest sedation level will be targeted, i.e. minimal to moderate sedation according to the US recommendations for sedation / analgesia. Systolic blood pressure will be maintained between 140 and 180 mmHg with an intravenous norepinephrine infusion if necessary and SpO2 will be maintained between 94 and 98%.	Procedure: Conscious Sedation A drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway. (From: American Society of Anesthesiologists Practice Guidelines)

Arm

Intervention/Treatment

Active Comparator: General anaesthesia

In the general anesthesia group, rapid sequence induction is used. Conduction of general anesthesia and drugs used are left to the expertise of each investigating center. Systolic blood pressure has to be maintained between 140 and 180 mmHg with an intravenous norepinephrine infusion if necessary, tele-expiratory carbon dioxyde concentration (EtCO2) has to be maintained between 30 and 35 mmHg and SpO2 has to be maintained between 94 and 98 %.

Procedure: General anaesthesia

Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery

Active Comparator: Conscious Sedation

In the conscious sedation group, drugs choice as well as pharmacological modulation will be left to the expertise of each investigating center. A sedation level between 0 and -3 with spontaneous breathing will be targeted, using the Richmond Agitation Sedation Scale (RASS) score validated in French. The lightest sedation level will be targeted, i.e. minimal to moderate sedation according to the US recommendations for sedation / analgesia. Systolic blood pressure will be maintained between 140 and 180 mmHg with an intravenous norepinephrine infusion if necessary and SpO2 will be maintained between 94 and 98%.

Procedure: Conscious Sedation

A drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway. (From: American Society of Anesthesiologists Practice Guidelines)

Outcome Measures

Primary Outcome Measures

composite of functional independence at 3 months and absence of medical complication occurring by day 7 after endovascular therapy for anterior circulation AIS [Day 90]
The primary outcome measure is a composite of functional independence at 3 months and absence of medical complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a mRS score 0 to 2 by day 90. Medical complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or acute cardiogenic pulmonary oedema or malignant stroke evolution occurring by day 7

Secondary Outcome Measures

Ordinal score on the mRS by day 90 [at day 90]
Functional independence by day 90 defined as a mRS score 0-2 [at day 90]
Excellent recovery by day 90 defined as a mRS score 0-1 [at day 90]
Moderate recovery by day 90 defined as a mRS score 0-3 [at day 90]
Shift analysis of day 90 mRS adjusted for initial prognostic factors [at day 90]
(baseline mRS, age, initial NIHSS, carotid top occlusion)
Good recovery defined with sliding dichotomy responder analysis relating day 90 mRS with baseline NIHSS score: mRS 0 for NIHSS ≤ 7; mRS 0-1 for NIHSS 8-14; mRS 0-2 for NIHSS > 14 [at day 90]
Intraprocedural hemodynamic and ventilatory conditions and complications defined as hypotension, blood pressure variability, hypoxemia and aspiration [at day 90]
Intervention-associated vessel and others complications defined as arterial dissection or perforation, groin hematoma, embolization in another arterial territory [at day 90]
Door to groin puncture delay [at day 90]
Door to reperfusion delay [at day 90]
Successful reperfusion defined by the modified Treatment In Cerebral Ischemia (mTICI) reperfusion scale of 2b or 3 (with a grade of 2b or 3 indicating reperfusion of > 50% of the affected territory) [at day 90]
NIHSS by day 1 and day 7 [by day 1 and day 7]
Stroke unit and hospital length of stay [at day 90]
Medical complications by day 7 defined as pneumonia, acute cardiogenic pulmonary oedema, myocardial infarction, extra pulmonary infection, venous thromboembolism, new event of AIS, epilepsy, gastrointestinal bleeding or other symptomatic bleeding [at day 7]
Malignant stroke evolution by day 7 [by day 7]
Symptomatic intracranial haemorrhage by day 7 defined as brain haemorrhage on imaging associated with an increase of at least 4 points in the NIHSS score [by day 7]
Unexpected intensive care unit admission by day 7 [by day 7]
Mortality by day 7 and day 90 [by day 7 and day 90]
Procedural feasibility score estimated by the radiologist and the anaesthesiologist and patient acceptability score [by day 7 and day 90]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Acute anterior circulation ischemic stroke (terminal portion of the internal carotid artery, middle cerebral artery), with indication for radiological mechanical thrombectomy assessed by the neurology / neuroradiology team
Over 18 years of age
Benefiting from an affiliation to the French Social Security system
Patient or familly informed consent. In case of patient incapacity and no family present, and due to the emergency of the procedure, the patient may be included on the sole decision of the investigator (emergency procedure with subsequent differed consent).

Exclusion Criteria:

Altered vigilance defined by score ≥ 2 at item 1a "level of consciousness" of the NIHSS score
Altered previous autonomy, defined by a modified Rankin score (mRS)> 1
Acute ischemic stroke of posterior circulation or anterior cerebral artery
Associated brain haemorrhage
Pregnant or nursing women
Patient under law protection
Stroke complicating another acute illness or postoperative stroke.