<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03229148</url>
  </required_header>
  <id_info>
    <org_study_id>CHU-343</org_study_id>
    <secondary_id>2017-0303001-90</secondary_id>
    <nct_id>NCT03229148</nct_id>
  </id_info>
  <brief_title>Anesthesia Management in Endovascular Therapy for Ischemic Stroke</brief_title>
  <acronym>AMETIS</acronym>
  <official_title>Anesthesia Management in Endovascular Therapy for Ischemic Stroke: A Multicenter Randomised Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Direction Générale de l'Offre de Soins</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Clermont-Ferrand</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objective of the study: to assess whether pharmacological sedation or general anesthesia for&#xD;
      treatment of anterior circulation ischemic stroke with endovascular mechanical thrombectomy&#xD;
      is associated with difference in morbidity (neurological outcome and peri-procedural&#xD;
      complications).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Since 2015, the management of anterior acute ischemic stroke (AIS) involves endovascular&#xD;
      treatment with mechanical thrombectomy (MT). This urgent, difficult and uncomfortable&#xD;
      procedure in frail patients requires multidisciplinary care ideally involving neurologists,&#xD;
      interventional neuroradiologists and anesthesiologists.&#xD;
&#xD;
      Two anesthetic strategies are currently used: pharmacologic sedation in spontaneous&#xD;
      ventilation or general anesthesia with tracheal intubation. General anesthesia provides&#xD;
      strict immobility, protects the airway and avoids emergency intubation in case of severe&#xD;
      procedural complication (notably vomiting and aspiration). Sedation is a frequently used&#xD;
      alternative because of (1) a rapid execution which could reduce delay to reperfusion, (2) a&#xD;
      lower risk of blood pressure drop that may compromise cerebral blood flow in the penumbra&#xD;
      area, (3) the theoretical capacity to assess neurological status during the procedure and (4)&#xD;
      the supposed risk of complications associated with mechanical ventilation and intravenous&#xD;
      anesthestics on brain metabolism. Nevertheless, sedation exposes to dramatic complications in&#xD;
      case of patient agitation and movements.&#xD;
&#xD;
      The choice of the ideal anesthesic management is still lacking. Old retrospective studies&#xD;
      seemed to favor sedation with worst neurological outcome associated with general anesthesia.&#xD;
      Nevertheless, these datas suffered methodological issues with selection bias: more severe&#xD;
      patients based on NIHSS score were rather treated with general anesthesia and blood pressure&#xD;
      was not controlled. Recent studies that demonstrated the benefit of MT did not include a&#xD;
      specific anesthetic protocol and none of the studies currently available included a blood&#xD;
      pressure management protocol that appears to be an essential component of cerebral perfusion.&#xD;
      A subgroup analysis of the MR Clean study, including patients with an identical initial NIHSS&#xD;
      score, did not find benefit from MT in patients with general anesthesia compared to those&#xD;
      receiving sedation. Finally, authors concluded that performing a MT under general anesthesia&#xD;
      would significantly lengthen the reperfusion delay and nullify the benefit of MT.&#xD;
&#xD;
      The prospective, randomized, single-center SIESTA trial, conducted in 150 patients with an&#xD;
      anterior circulation AIS, found no difference in the early neurological improvement (primary&#xD;
      endpoint), assessed on the change in NIHSS score between admission and the 24th hour, between&#xD;
      the conscious sedation group and the general anesthesia group. There were a tendency for a&#xD;
      better 3-month neurological outcome in the general anesthesia group (37% vs 18% of patients&#xD;
      with a Modified Rankin score of 0-2 in the general anesthesia and conscious sedation groups&#xD;
      respectively), but it was not possible to conclude due to a lack of statistical power.&#xD;
&#xD;
      Due to the increasing number of patients eligible for endovascular MT and the potential&#xD;
      implication of these two anesthetic management on the functional outcome, a study comparing&#xD;
      general anesthesia and sedation during a MT seems essential as specified in the recent&#xD;
      updated American Stroke Association guidelines.&#xD;
&#xD;
      The objective of this study is to assess whether sedation or general anesthesia during&#xD;
      endovascular treatment with mechanical thrombectomy is associated with a difference in&#xD;
      morbidity (neurological outcome and peri-procedural complications), in anterior circulation&#xD;
      AIS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2017</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">May 13, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Multicentic, prospective, open, in parallel groups, stratified and randomised study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>composite of functional independence at 3 months and absence of medical complication occurring by day 7 after endovascular therapy for anterior circulation AIS</measure>
    <time_frame>Day 90</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ordinal score on the mRS by day 90</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional independence by day 90 defined as a mRS score 0-2</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Excellent recovery by day 90 defined as a mRS score 0-1</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Moderate recovery by day 90 defined as a mRS score 0-3</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Shift analysis of day 90 mRS adjusted for initial prognostic factors</measure>
    <time_frame>at day 90</time_frame>
    <description>(baseline mRS, age, initial NIHSS, carotid top occlusion)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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 &gt; 14</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraprocedural hemodynamic and ventilatory conditions and complications defined as hypotension, blood pressure variability, hypoxemia and aspiration</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intervention-associated vessel and others complications defined as arterial dissection or perforation, groin hematoma, embolization in another arterial territory</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Door to groin puncture delay</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Door to reperfusion delay</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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 &gt; 50% of the affected territory)</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIHSS by day 1 and day 7</measure>
    <time_frame>by day 1 and day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke unit and hospital length of stay</measure>
    <time_frame>at day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>at day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Malignant stroke evolution by day 7</measure>
    <time_frame>by day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>by day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unexpected intensive care unit admission by day 7</measure>
    <time_frame>by day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality by day 7 and day 90</measure>
    <time_frame>by day 7 and day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedural feasibility score estimated by the radiologist and the anaesthesiologist and patient acceptability score</measure>
    <time_frame>by day 7 and day 90</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">332</enrollment>
  <condition>Stroke</condition>
  <condition>Thrombectomy</condition>
  <condition>Anesthesia</condition>
  <condition>Conscious Sedation</condition>
  <arm_group>
    <arm_group_label>General anaesthesia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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 %.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conscious Sedation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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%.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>General anaesthesia</intervention_name>
    <description>Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery</description>
    <arm_group_label>General anaesthesia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Conscious Sedation</intervention_name>
    <description>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)</description>
    <arm_group_label>Conscious Sedation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Acute anterior circulation ischemic stroke (terminal portion of the internal carotid&#xD;
             artery, middle cerebral artery), with indication for radiological mechanical&#xD;
             thrombectomy assessed by the neurology / neuroradiology team&#xD;
&#xD;
          -  Over 18 years of age&#xD;
&#xD;
          -  Benefiting from an affiliation to the French Social Security system&#xD;
&#xD;
          -  Patient or familly informed consent. In case of patient incapacity and no family&#xD;
             present, and due to the emergency of the procedure, the patient may be included on the&#xD;
             sole decision of the investigator (emergency procedure with subsequent differed&#xD;
             consent).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Altered vigilance defined by score ≥ 2 at item 1a &quot;level of consciousness&quot; of the&#xD;
             NIHSS score&#xD;
&#xD;
          -  Altered previous autonomy, defined by a modified Rankin score (mRS)&gt; 1&#xD;
&#xD;
          -  Acute ischemic stroke of posterior circulation or anterior cerebral artery&#xD;
&#xD;
          -  Associated brain haemorrhage&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Patient under law protection&#xD;
&#xD;
          -  Stroke complicating another acute illness or postoperative stroke.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Russel Chabanne, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU de Clermont-Ferrand</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <state>Auvergne</state>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17. Erratum In: N Engl J Med. 2015 Jan 22;372(4):394.</citation>
    <PMID>25517348</PMID>
  </reference>
  <reference>
    <citation>Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.</citation>
    <PMID>25671798</PMID>
  </reference>
  <reference>
    <citation>Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.</citation>
    <PMID>25882376</PMID>
  </reference>
  <reference>
    <citation>Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.</citation>
    <PMID>25882510</PMID>
  </reference>
  <reference>
    <citation>Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.</citation>
    <PMID>25671797</PMID>
  </reference>
  <reference>
    <citation>Berkhemer OA, van den Berg LA, Fransen PS, Beumer D, Yoo AJ, Lingsma HF, Schonewille WJ, van den Berg R, Wermer MJ, Boiten J, Lycklama A Nijeholt GJ, Nederkoorn PJ, Hollmann MW, van Zwam WH, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW, Roos YB; MR CLEAN investigators. The effect of anesthetic management during intra-arterial therapy for acute stroke in MR CLEAN. Neurology. 2016 Aug 16;87(7):656-64. doi: 10.1212/WNL.0000000000002976. Epub 2016 Jul 15.</citation>
    <PMID>27421546</PMID>
  </reference>
  <reference>
    <citation>Schonenberger S, Uhlmann L, Hacke W, Schieber S, Mundiyanapurath S, Purrucker JC, Nagel S, Klose C, Pfaff J, Bendszus M, Ringleb PA, Kieser M, Mohlenbruch MA, Bosel J. Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial. JAMA. 2016 Nov 15;316(19):1986-1996. doi: 10.1001/jama.2016.16623. Erratum In: JAMA. 2017 Feb 7;317(5):538.</citation>
    <PMID>27785516</PMID>
  </reference>
  <reference>
    <citation>Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, Johnston KC, Johnston SC, Khalessi AA, Kidwell CS, Meschia JF, Ovbiagele B, Yavagal DR; American Heart Association Stroke Council. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015 Oct;46(10):3020-35. doi: 10.1161/STR.0000000000000074. Epub 2015 Jun 29.</citation>
    <PMID>26123479</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>September 28, 2020</last_update_submitted>
  <last_update_submitted_qc>September 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anesthesia or Conscious sedation for Thrombectomy for Stroke</keyword>
  <keyword>Thrombectomy</keyword>
  <keyword>Anesthesia</keyword>
  <keyword>Conscious sedation</keyword>
  <keyword>Stroke</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03229148
org study id: CHU-343
secondary id: 2017-0303001-90
nct id: NCT03229148
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
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).
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multicentic, prospective, open, in parallel groups, stratified and randomised study.
primary purpose: Treatment
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.
measure: 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
description: 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
measure: Ordinal score on the mRS by day 90
time frame: at day 90
measure: Functional independence by day 90 defined as a mRS score 0-2
time frame: at day 90
measure: Excellent recovery by day 90 defined as a mRS score 0-1
time frame: at day 90
measure: Moderate recovery by day 90 defined as a mRS score 0-3
time frame: at day 90
measure: Shift analysis of day 90 mRS adjusted for initial prognostic factors
time frame: at day 90
description: (baseline mRS, age, initial NIHSS, carotid top occlusion)
measure: 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
measure: Intraprocedural hemodynamic and ventilatory conditions and complications defined as hypotension, blood pressure variability, hypoxemia and aspiration
time frame: at day 90
measure: Intervention-associated vessel and others complications defined as arterial dissection or perforation, groin hematoma, embolization in another arterial territory
time frame: at day 90
measure: Door to groin puncture delay
time frame: at day 90
measure: Door to reperfusion delay
time frame: at day 90
measure: 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
measure: NIHSS by day 1 and day 7
time frame: by day 1 and day 7
measure: Stroke unit and hospital length of stay
time frame: at day 90
measure: 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
measure: Malignant stroke evolution by day 7
time frame: by day 7
measure: 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
measure: Unexpected intensive care unit admission by day 7
time frame: by day 7
measure: Mortality by day 7 and day 90
time frame: by day 7 and day 90
measure: Procedural feasibility score estimated by the radiologist and the anaesthesiologist and patient acceptability score
time frame: by day 7 and day 90
arm group label: General anaesthesia
arm group type: Active Comparator
description: 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 %.
arm group label: Conscious Sedation
arm group type: Active Comparator
description: 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 type: Procedure
intervention name: General anaesthesia
description: Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery
arm group label: General anaesthesia
intervention type: Procedure
intervention name: Conscious Sedation
description: 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 group label: Conscious Sedation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Russel Chabanne, MD
role: Principal Investigator
affiliation: CHU de Clermont-Ferrand
facility: 
country: France
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PMID: 25517348
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PMID: 25671798
citation: Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.
PMID: 25882376
citation: Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.
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PMID: 25671797
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PMID: 27421546
citation: Schonenberger S, Uhlmann L, Hacke W, Schieber S, Mundiyanapurath S, Purrucker JC, Nagel S, Klose C, Pfaff J, Bendszus M, Ringleb PA, Kieser M, Mohlenbruch MA, Bosel J. Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial. JAMA. 2016 Nov 15;316(19):1986-1996. doi: 10.1001/jama.2016.16623. Erratum In: JAMA. 2017 Feb 7;317(5):538.
PMID: 27785516
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PMID: 26123479
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Anesthetics