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Anesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03229148
Recruitment Status : Completed
First Posted : July 25, 2017
Last Update Posted : September 30, 2020
Sponsor:
Collaborator:
Direction Générale de l'Offre de Soins
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand

Tracking Information
First Submitted Date  ICMJE July 20, 2017
First Posted Date  ICMJE July 25, 2017
Last Update Posted Date September 30, 2020
Actual Study Start Date  ICMJE August 31, 2017
Actual Primary Completion Date May 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 28, 2020)
composite of functional independence at 3 months and absence of medical complication occurring by day 7 after endovascular therapy for anterior circulation AIS [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: July 24, 2017)
patients with an altered neurological outcome at day 90 or a serious complication within 7 days post-procedure [ Time Frame: on day 7 and day 90 ]
A composite judgment criterion evaluating the proportion of patients with an altered neurological outcome (Modified Rankin scale > 2) at day 90 and / or a serious complication within 7 days post-procedure among: Procedural radiological complication: perforation or arterial dissection, Pulmonary complication: infectious broncho-pneumonia, Cardiovascular complication: myocardial infarction, acute heart failure, Neurological complication: "malignant" transformation of stroke
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2019)
  • Ordinal score on the mRS by day 90 [ Time Frame: at day 90 ]
  • Functional independence by day 90 defined as a mRS score 0-2 [ Time Frame: at day 90 ]
  • Excellent recovery by day 90 defined as a mRS score 0-1 [ Time Frame: at day 90 ]
  • Moderate recovery by day 90 defined as a mRS score 0-3 [ Time Frame: at day 90 ]
  • Shift analysis of day 90 mRS adjusted for initial prognostic factors [ Time Frame: 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 [ Time Frame: at day 90 ]
  • Intraprocedural hemodynamic and ventilatory conditions and complications defined as hypotension, blood pressure variability, hypoxemia and aspiration [ Time Frame: at day 90 ]
  • Intervention-associated vessel and others complications defined as arterial dissection or perforation, groin hematoma, embolization in another arterial territory [ Time Frame: at day 90 ]
  • Door to groin puncture delay [ Time Frame: at day 90 ]
  • Door to reperfusion delay [ Time Frame: 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) [ Time Frame: at day 90 ]
  • NIHSS by day 1 and day 7 [ Time Frame: by day 1 and day 7 ]
  • Stroke unit and hospital length of stay [ Time Frame: 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 [ Time Frame: at day 7 ]
  • Malignant stroke evolution by day 7 [ Time Frame: 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 [ Time Frame: by day 7 ]
  • Unexpected intensive care unit admission by day 7 [ Time Frame: by day 7 ]
  • Mortality by day 7 and day 90 [ Time Frame: by day 7 and day 90 ]
  • Procedural feasibility score estimated by the radiologist and the anaesthesiologist and patient acceptability score [ Time Frame: by day 7 and day 90 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2017)
  • Modified Rankin Scale [ Time Frame: at day 90 ]
  • NIHSS score [ Time Frame: at 24 hours of the procedure and at day 7 ]
  • Maximum difference in systolic blood pressure (SBP) during the procedure [ Time Frame: at day 90 ]
    as defined by the difference between the maximum SBP before procedure and the minimum SBP during the procedure
  • Area under the mean arterial pressure curve [ Time Frame: at day 90 ]
  • Area under the curve of pulsed oxygen saturation [ Time Frame: at day 90 ]
  • Arterial perforation per procedure [ Time Frame: at day 90 ]
  • Arterial dissection per procedure [ Time Frame: at day 90 ]
  • "Stroke / arterial puncture " delay in minutes [ Time Frame: at day 1 ]
  • "Stroke / reperfusion " delay in minutes [ Time Frame: at day 1 ]
  • TICI recanalization score [ Time Frame: at day 1 ]
  • Myocardial infarction [ Time Frame: at day 7 ]
  • Infectious Broncho-Pneumonia [ Time Frame: at day 7 ]
  • Acute cardiac failure with pulmonary edema [ Time Frame: at day 7 ]
  • "Malignant" transformation of stroke [ Time Frame: at day 7 ]
    defined by the occurrence of a mass effect related to a large cerebral infarction requiring medical and / or surgical treatment (craniectomy)
  • Symptomatic cerebral haemorrhage [ Time Frame: at day 7 ]
    defined by the occurrence of neurological deterioration in relation to intracranial or meningeal haemorrhage
  • Hospital length of stay [ Time Frame: at day 1 ]
  • stroke center length of stay [ Time Frame: at day 1 ]
  • Hospitalization in intensive care unit [ Time Frame: at day 7 ]
  • Mortality [ Time Frame: on day 7 and day 90 ]
  • Procedural Feasibility score estimated by the radiologist [ Time Frame: at day 7 ]
  • Feasibility score estimated by the anesthesiologist [ Time Frame: at day 7 ]
  • Acceptability score estimated by the patient [ Time Frame: at day 7 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anesthesia Management in Endovascular Therapy for Ischemic Stroke
Official Title  ICMJE Anesthesia Management in Endovascular Therapy for Ischemic Stroke: A Multicenter Randomised Study
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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
Condition  ICMJE
  • Stroke
  • Thrombectomy
  • Anesthesia
  • Conscious Sedation
Intervention  ICMJE
  • 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
  • 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)
Study Arms  ICMJE
  • 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 %.
    Intervention: Procedure: General anaesthesia
  • 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%.
    Intervention: Procedure: Conscious Sedation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 2, 2020)
332
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2017)
270
Actual Study Completion Date  ICMJE June 30, 2020
Actual Primary Completion Date May 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03229148
Other Study ID Numbers  ICMJE CHU-343
2017-0303001-90 ( Other Identifier: 2017-0303001-90 )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Clermont-Ferrand
Study Sponsor  ICMJE University Hospital, Clermont-Ferrand
Collaborators  ICMJE Direction Générale de l'Offre de Soins
Investigators  ICMJE
Principal Investigator: Russel Chabanne, MD CHU de Clermont-Ferrand
PRS Account University Hospital, Clermont-Ferrand
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP