<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/NCT03247998</url>
  </required_header>
  <id_info>
    <org_study_id>GA Stroke</org_study_id>
    <nct_id>NCT03247998</nct_id>
  </id_info>
  <brief_title>GA vs. CS for Endovascular Stroke Therapy</brief_title>
  <official_title>GASTROKE- the Effect of General Anesthesia Versus Sedation for Patients With Acute Ischemic STROKE Undergoing Endovascular Treatment on Three Month Morbidity and Mortality: a Feasibility Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lawson Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lawson Health Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      After a stroke caused by a blockage (clot) in a blood vessel in the brain, patients may have&#xD;
      the clot removed by threading a catheter from the groin up to the affected area of the brain.&#xD;
      An anesthesiologist is involved in the patient's care during this procedure to maximize&#xD;
      patient safety and procedural efficiency. The options for anesthesia for this procedure are&#xD;
      general anesthesia (where the patient is unconscious) or sedation (where the patient is in a&#xD;
      relaxed, calm, sleepy condition). Currently, it is unclear which of these anesthetic options&#xD;
      contributes to the best patient outcome. The investigators would like to investigate whether&#xD;
      or not one method of anesthesia (general or sedation) is better to use than the other when&#xD;
      removing the clot.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Stroke is a leading cause of adult morbi-mortality worldwide. Intravenous (IV)&#xD;
      recombinant tissue plasminogen activator (rtTPA) was the only therapeutic option for many&#xD;
      years. After the publication of five randomized controlled trials, guidelines for stroke&#xD;
      treatment were updated and released in 2015. According to these guidelines, in addition to IV&#xD;
      rtTPA, endovascular therapy (EVT) for acute ischemic stroke (AIS), secondary to proximal&#xD;
      intracranial arterial occlusion, has become established as an international standard of care&#xD;
      (Avitsian &amp; Machado, 2016). Management of patients undergoing stroke is complex due to the&#xD;
      association of acute neurological physiological changes and pre-existing co-morbidities. To&#xD;
      facilitate efficient and safe delivery of endovascular treatment, patients require anesthetic&#xD;
      intervention in the form of sedation or general anesthesia (GA). The choice of anesthetic&#xD;
      technique is often guided by individual patient factors and personal clinician practice&#xD;
      (Dhakal, Diaz-Gomez, &amp; Freeman, 2015). Two recent meta-analyses (Brinjikji et al., 2015) have&#xD;
      found an association of better functional outcome related to endovascular procedures&#xD;
      performed under sedation compared to general anesthesia. The interpretation of current data&#xD;
      is challenging as most studies are retrospective and performed under direction of&#xD;
      non-anesthetists with poor definition of anesthetic techniques. A prospective controlled&#xD;
      randomized trial is required to demonstrate the influence of anesthesia techniques on&#xD;
      functional outcome. Prior to commencing this large trial, the investigators will execute a&#xD;
      feasibility study (GASTROKE-pilot), which is outlined here. Following confirmation of&#xD;
      feasibility, the full prospective randomized controlled trial will take place using the same&#xD;
      study methodology.&#xD;
&#xD;
      The objectives of the pilot study are: 1) To determine feasibility of the methods and&#xD;
      procedures for a proposed prospective randomized controlled trial. Specifically, to determine&#xD;
      if randomization can be reliably performed in a timely fashion to facilitate inclusion in the&#xD;
      study. Note: EVT will not be delayed beyond institutional temporal limits to allow&#xD;
      recruitment or randomization of potential participants. 2) To determine if anesthesia for EVT&#xD;
      can be reliably delivered according to the standardized protocol. 3) To determine if&#xD;
      post-treatment follow-up of functional outcome can be reliably performed according to a&#xD;
      standardized methodology. If the pilot study demonstrates feasibility, the investigators will&#xD;
      proceed with a much larger RCT.&#xD;
&#xD;
      Methodology: Randomization: Patients identified by the Acute Stroke team as candidates for&#xD;
      EVT will be referred to the study anesthesia team for consideration as study participants.&#xD;
      Only after anesthetic pre-procedural assessment is complete, as per usual standard of care,&#xD;
      and clinical uncertainty exists as to the best anesthetic management will the patient be&#xD;
      randomized. Sequence generation: Randomization will be performed using REDCap to allow&#xD;
      central randomization from any hospital computer with internet access. The blocked&#xD;
      randomization sequence list will be created in STATA. The randomization instrument will be&#xD;
      created in REDCap separate to the data collection tool to ensure blinding allocation is&#xD;
      maintained. All treating consultant anesthetists will have access to the REDCap randomization&#xD;
      instrument. User rights will be set so that these clinicians do not have access to&#xD;
      participant follow-up data. Details of each procedure (GA or sedation) are outlined below.&#xD;
      The attending anesthetist will log-on to REDCap and access the Randomization tool. This&#xD;
      process will take 2-3 minutes once trained in the randomization process.&#xD;
&#xD;
      Blinding: Both patient and treating physician will be aware of the treatment assignment.&#xD;
      Post-procedural functional outcomes will be performed by a dedicated clinician blinded to the&#xD;
      treatment assignment. Interventions: Physiological Parameters: Target Values (Talke et al.,&#xD;
      2014) • Oxygenation: Maintain SpO2 &gt; 92% and PaO2 &gt; 60 mmHg. • Ventilation: Maintain&#xD;
      normocapnia, PaCO2 35-45 mmHg under GA. Avoid respiratory-induced hypercarbia during sedation&#xD;
      • Hemodynamics: Systolic blood pressure &gt; 140 mmHg and &lt; 180 mmHg. Diastolic blood pressure &lt;&#xD;
      105 mmHg. • Temperature: Maintain normothermia, T 35°C - 37°C. • Glucose control: Maintain&#xD;
      blood glucose concentration 4.0 - 8.0 mmol/L. If blood glucose levels greater than 8 mmol/L&#xD;
      (140 mg/dL) IV insulin infusion to be commenced. Blood glucose concentration to be repeated&#xD;
      after 30 minutes. Hypoglycemia as defined by blood glucose &lt; 3 mmol/L (50 mg/dL) should be&#xD;
      treated with IV 10-20% glucose. General Anesthesia Protocol: (Melinda J. Davis, Cynthia R.&#xD;
      Campos-Herrera, &amp; David P. Archer, 2012; Powers et al., 2015; Talke et al., 2014) 1.&#xD;
      Monitoring • American Society of Anesthesiologists (ASA) standard (non-invasive blood&#xD;
      pressure (BP), electrocardiogram (ECG), oxygen saturation (SpO2), end-tidal carbon dioxide&#xD;
      (ETCO2), temperature and neuromuscular monitoring (NMM)) • Invasive BP: direct measure of the&#xD;
      arterial BP, with continuous pressure transduction and waveform display is the standard for&#xD;
      blood pressure monitoring in AIS. It allows continuous BP assessment and provides reliable&#xD;
      vascular access for frequent sampling. However, benefits of invasive arterial monitoring are&#xD;
      null if the procedure itself delays reperfusion therapy (Saver, 2006). There is no consensus&#xD;
      regarding timing of arterial access in EVT for AIS. This is our protocol: • 1 attempt with&#xD;
      the patient awake • Maximum of 2 more attempts with the patient under anesthesia • Stop after&#xD;
      a total of 3 attempts, or when the radiologist has access to the femoral artery. 2. Induction&#xD;
      of anesthesia. 3. Neuromuscular paralysis. 4. Endotracheal intubation. 5. Positive pressure&#xD;
      ventilation: ETCO2 range: 35-40 mmHg until arterial partial pressure of carbon dioxide&#xD;
      (PaCO2) is obtained and the gap is measured. 6. Volatile anesthesia with sevoflurane or&#xD;
      desflurane to a target age-compensated minimum alveolar concentration (MAC) &gt; 0.5 but =&#xD;
      1(Sivasankar et al., 2016) 7. Vasopressor support: If the systolic BP decreases more than 20%&#xD;
      from pre-anesthetic value or is lower than 140 mmHg, the patient will receive vasopressor&#xD;
      support as IV phenylephrine and/or ephedrine, titrated to effect. 8. Hypertension management:&#xD;
      For systolic BP &gt; 180 mmHg, IV labetalol will be administered, titrated to effect. 9.&#xD;
      Arterial blood gas sampling to be performed at the earliest convenience after induction of&#xD;
      anesthesia. Clinical goals are outlined above. 10. Temperature monitoring wit esophageal&#xD;
      temperature probe. 11. Antagonism of neuromuscular blockade at the end of the procedure. The&#xD;
      train of four should be = 0.9 prior to extubation (Hassan et al., 2012; Murphy GS, 2015). 12.&#xD;
      Transfer the patient to the post-anesthesia care unit (PACU). Sedation Protocol: 1.&#xD;
      Monitoring • ASA standard (non-invasive BP, ECG, SpO2, T, respiratory rate (RR), and ETCO2) •&#xD;
      Invasive BP: a direct measure of the arterial blood pressure, • Maximum 3 attempts. Stop&#xD;
      after a total of 3 attempts, or when the radiologist has access to the femoral artery. 2.&#xD;
      Administer oxygen by nasal prongs or facial mask to achieve a target Sp02 = 92%. 3. Commence&#xD;
      sedation: Remifentanil: 0.01-0.06 micrograms/kilogram/minute, titrated to effect. (Janssen et&#xD;
      al., 2016) 4. Monitor RR. Decrease sedative infusion rate if RR &lt; 6. 5. Vasopressor support:&#xD;
      If the systolic BP decreases more than 20% from pre-anesthetic value or if is lower than 140&#xD;
      mmHg, the patient will receive vasopressor support as IV phenylephrine and/or ephedrine,&#xD;
      titrated to effect. 6. Hypertension management: For systolic BP &gt; 180 mmHg, IV labetalol will&#xD;
      be administered, titrated to effect. 7. Arterial blood gas sampling to be performed at the&#xD;
      earliest convenience after induction of anesthesia. Clinical goals are outlined above. 8.&#xD;
      Temperature monitoring with axillary temperature probe. 9. Transfer the patient to the PACU.&#xD;
&#xD;
      Conversion of sedation to GA: Patients randomized to receive EVT under sedation will be&#xD;
      converted to GA in cases of emergency (vascular injury), reduced level of consciousness&#xD;
      (GCS&lt;8), loss of airway reflexed, respiratory failure with rise in EtCO2 and agitation&#xD;
      precluding safe conduct of EVT.&#xD;
&#xD;
      Post-Procedural Follow-up:This will be conducted by a clinical research assistant who is&#xD;
      blinded to the study intervention. The specifics of the follow-up procedure are detailed&#xD;
      below: Day1: The NIHSS clinical scoring tool will be performed on the stoke inpatient unit.&#xD;
      This scale is a validated tool to objectively quantify disability following a stroke. The&#xD;
      tool entails assessment of level of consciousness, motor function, sensation, coordination,&#xD;
      speech and concentration. Currently, this tool is utilised at LHSC as part of the follow-up&#xD;
      for AIS post-procedural days 1. Day 1-2: All patients will have a CT angiogram and MRI within&#xD;
      24-48 hours post-procedure as per usual standard of care. From these scans, the Thrombolysis&#xD;
      in Cerebral Infarction (TICI) scale and final infarct volume will be calculated. Day 7: The&#xD;
      NIHSS will be repeated to quantify ongoing disability. Day 90: As per the usual standard of&#xD;
      care, all patient discharged from hospital will have a 3 month post-stroke outpatient&#xD;
      follow-up appointment. The mRS and NIHSS will be repeated by the clinical research assistant&#xD;
      at the neurological outpatient appointment. Should the appointment be delayed longer than 3&#xD;
      months post-stroke, a telephone call will be made by the clinical research assistant to&#xD;
      determine the mRS. If the patient remains an inpatient at 90 days post-stroke, the electronic&#xD;
      record will be accessed to gain the required information to calculate the mRS&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 31, 2017</start_date>
  <completion_date type="Anticipated">August 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2019</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>There will be two arms of this study. In the first arm, the patients who meet the inclusion criteria of the study will be randomized to receive general anesthesia during endovascular treatment for stroke. In the second arm of the study, patients will receive general sedation during endovascular treatment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The outcomes assessor who will analyze the outcome variables for this study (consciousness, motor function, sensation, speech, coordination, standard of care follow up assessments etc.) that may be impacted by choice of anesthesia/analgesia will be blinded to the treatment group of the participants to ensure unbiased reporting.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Randomization potential</measure>
    <time_frame>20 weeks</time_frame>
    <description>Total number of participants that have been recruited and the drop out rates. Recruitment goal is 20 patients within 20 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants that complete the recruitment procedure prior to start of endovascular treatment.</measure>
    <time_frame>20 weeks</time_frame>
    <description>These procedures include patient identification and baseline assessments such as patient co-morbidities, demographics, and pre-procedural anesthetic assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of time to complete/completeness of study-related assessments</measure>
    <time_frame>1 year</time_frame>
    <description>To assess the feasibility of obtaining completed follow up assessments with this patient population and the time it takes to accomplish this.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Stroke</condition>
  <condition>Endovascular Repair</condition>
  <condition>Anesthesia</condition>
  <arm_group>
    <arm_group_label>General Anesthesia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who have had a stroke and meet the inclusion criteria for the study will receive general anesthesia during endovascular treatment. Choice of anesthetic for general anesthesia is dependent upon the patient condition and decision of the treating anesthesiologist (ketamine, propofol, fentanyl, midazolam,dexmedetomidine etc.). General Anesthesia Protocol: (Melinda J. Davis, Cynthia R. Campos-Herrera, &amp; David P. Archer, 2012; Powers et al., 2015; Talke et al., 2014). Patient will be monitored in accordance with standard monitoring guidelines and the rest of the procedure will proceed in accordance with standard of care.&#xD;
See Detailed Description for additional details and description of follow-up procedures.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conscious Sedation with Remifentanil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who have had a stroke and meet the inclusion criteria for the study will receive conscious during endovascular treatment. Sedation will be accomplished using Remifentanil: 0.01-0.06 micrograms/kilogram/minute, titrated to effect. (Janssen et al., 2016). Patients who have had a stroke and meet the inclusion criteria for the study will receive general anesthesia during endovascular treatment. Patient will be monitored in accordance with standard monitoring guidelines and the rest of the procedure will proceed in accordance with standard of care.&#xD;
See Detailed Description for additional details and description of follow-up procedures.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>General Anesthesia</intervention_name>
    <description>Patients who have had a stroke and meet the inclusion criteria for the study will receive general anesthesia during endovascular treatment. Choice of anesthetic for general anesthesia is dependent upon the patient condition and decision of the treating anesthesiologist (ketamine, propofol, fentanyl, midazolam,dexmedetomidine etc.). Induction of general anesthesia will follow standard treatment methods (Davis et al, 2012, Powers et al. 2015 Talke et al. 2015). Patient monitoring and care will proceed in accordance with standard of care guidelines. Refer to Detailed Description section for complete protocol information.</description>
    <arm_group_label>General Anesthesia</arm_group_label>
    <other_name>No other names</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Conscious Sedation with Remifentanil</intervention_name>
    <description>Patients who have had a stroke and meet the inclusion criteria for the study will receive conscious during endovascular treatment. Sedation will be accomplished using Remifentanil: 0.01-0.06 micrograms/kilogram/minute, titrated to effect. (Janssen et al., 2016). Patient monitoring and care will proceed in accordance with standard of care guidelines. Refer to Detailed Description section for complete protocol information.</description>
    <arm_group_label>Conscious Sedation with Remifentanil</arm_group_label>
    <other_name>No other names</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: All patients with ischemic stroke who:&#xD;
&#xD;
          -  are greater than 18 years of age&#xD;
&#xD;
          -  considered to be a candidate for endovascular therapy by the London Health Sciences&#xD;
             Stroke team&#xD;
&#xD;
          -  presenting within the first 8 hours after symptom onset EXCEPT THOSE for whom general&#xD;
             anesthesia is thought to be clearly indicated or contraindicated, by the attending&#xD;
             anesthesiologist.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients in whom the attending anesthesiologist considered that there was a clear&#xD;
             indication for either GA or sedation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Miguel Arango</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lawson Health Research Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Miguel Arango</last_name>
    <phone>519-685-8500</phone>
    <phone_ext>35571</phone_ext>
    <email>miguel.arango@lhsc.on.ca</email>
  </overall_contact>
  <reference>
    <citation>Avitsian R, Machado SB. Anesthesia for Endovascular Approaches to Acute Ischemic Stroke. Anesthesiol Clin. 2016 Sep;34(3):497-509. doi: 10.1016/j.anclin.2016.04.004.</citation>
    <PMID>27521194</PMID>
  </reference>
  <reference>
    <citation>Brinjikji W, Murad MH, Rabinstein AA, Cloft HJ, Lanzino G, Kallmes DF. Conscious sedation versus general anesthesia during endovascular acute ischemic stroke treatment: a systematic review and meta-analysis. AJNR Am J Neuroradiol. 2015 Mar;36(3):525-9. doi: 10.3174/ajnr.A4159. Epub 2014 Nov 13.</citation>
    <PMID>25395655</PMID>
  </reference>
  <reference>
    <citation>Dhakal LP, Diaz-Gomez JL, Freeman WD. Role of anesthesia for endovascular treatment of ischemic stroke: do we need neurophysiological monitoring? Stroke. 2015 Jun;46(6):1748-54. doi: 10.1161/STROKEAHA.115.008223. Epub 2015 May 7. No abstract available.</citation>
    <PMID>25953376</PMID>
  </reference>
  <reference>
    <citation>Davis MJ, Menon BK, Baghirzada LB, Campos-Herrera CR, Goyal M, Hill MD, Archer DP; Calgary Stroke Program. Anesthetic management and outcome in patients during endovascular therapy for acute stroke. Anesthesiology. 2012 Feb;116(2):396-405. doi: 10.1097/ALN.0b013e318242a5d2.</citation>
    <PMID>22222475</PMID>
  </reference>
  <reference>
    <citation>Talke PO, Sharma D, Heyer EJ, Bergese SD, Blackham KA, Stevens RD. Republished: Society for Neuroscience in Anesthesiology and Critical Care expert consensus statement: Anesthetic management of endovascular treatment for acute ischemic stroke. Stroke. 2014 Aug;45(8):e138-50. doi: 10.1161/STROKEAHA.113.003412.</citation>
    <PMID>25070964</PMID>
  </reference>
  <reference>
    <citation>Janssen H, Buchholz G, Killer M, Ertl L, Bruckmann H, Lutz J. General Anesthesia Versus Conscious Sedation in Acute Stroke Treatment: The Importance of Head Immobilization. Cardiovasc Intervent Radiol. 2016 Sep;39(9):1239-44. doi: 10.1007/s00270-016-1411-5. Epub 2016 Jul 7.</citation>
    <PMID>27387186</PMID>
  </reference>
  <reference>
    <citation>Sivasankar C, Stiefel M, Miano TA, Kositratna G, Yandrawatthana S, Hurst R, Kofke WA. Anesthetic variation and potential impact of anesthetics used during endovascular management of acute ischemic stroke. J Neurointerv Surg. 2016 Nov;8(11):1101-1106. doi: 10.1136/neurintsurg-2015-011998. Epub 2015 Nov 27.</citation>
    <PMID>26614493</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>August 9, 2017</last_update_submitted>
  <last_update_submitted_qc>August 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lawson Health Research Institute</investigator_affiliation>
    <investigator_full_name>Miguel Arango</investigator_full_name>
    <investigator_title>Anesthesiologist, Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Stroke</keyword>
  <keyword>endovascular repair</keyword>
  <keyword>general anesthesia</keyword>
  <keyword>conscious sedation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Remifentanil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03247998
org study id: GA Stroke
nct id: NCT03247998
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
After a stroke caused by a blockage (clot) in a blood vessel in the brain, patients may have
      the clot removed by threading a catheter from the groin up to the affected area of the brain.
      An anesthesiologist is involved in the patient's care during this procedure to maximize
      patient safety and procedural efficiency. The options for anesthesia for this procedure are
      general anesthesia (where the patient is unconscious) or sedation (where the patient is in a
      relaxed, calm, sleepy condition). Currently, it is unclear which of these anesthetic options
      contributes to the best patient outcome. The investigators would like to investigate whether
      or not one method of anesthesia (general or sedation) is better to use than the other when
      removing the clot.
Rationale: Stroke is a leading cause of adult morbi-mortality worldwide. Intravenous (IV)
      recombinant tissue plasminogen activator (rtTPA) was the only therapeutic option for many
      years. After the publication of five randomized controlled trials, guidelines for stroke
      treatment were updated and released in 2015. According to these guidelines, in addition to IV
      rtTPA, endovascular therapy (EVT) for acute ischemic stroke (AIS), secondary to proximal
      intracranial arterial occlusion, has become established as an international standard of care
      (Avitsian & Machado, 2016). Management of patients undergoing stroke is complex due to the
      association of acute neurological physiological changes and pre-existing co-morbidities. To
      facilitate efficient and safe delivery of endovascular treatment, patients require anesthetic
      intervention in the form of sedation or general anesthesia (GA). The choice of anesthetic
      technique is often guided by individual patient factors and personal clinician practice
      (Dhakal, Diaz-Gomez, & Freeman, 2015). Two recent meta-analyses (Brinjikji et al., 2015) have
      found an association of better functional outcome related to endovascular procedures
      performed under sedation compared to general anesthesia. The interpretation of current data
      is challenging as most studies are retrospective and performed under direction of
      non-anesthetists with poor definition of anesthetic techniques. A prospective controlled
      randomized trial is required to demonstrate the influence of anesthesia techniques on
      functional outcome. Prior to commencing this large trial, the investigators will execute a
      feasibility study (GASTROKE-pilot), which is outlined here. Following confirmation of
      feasibility, the full prospective randomized controlled trial will take place using the same
      study methodology.

      The objectives of the pilot study are: 1) To determine feasibility of the methods and
      procedures for a proposed prospective randomized controlled trial. Specifically, to determine
      if randomization can be reliably performed in a timely fashion to facilitate inclusion in the
      study. Note: EVT will not be delayed beyond institutional temporal limits to allow
      recruitment or randomization of potential participants. 2) To determine if anesthesia for EVT
      can be reliably delivered according to the standardized protocol. 3) To determine if
      post-treatment follow-up of functional outcome can be reliably performed according to a
      standardized methodology. If the pilot study demonstrates feasibility, the investigators will
      proceed with a much larger RCT.

      Methodology: Randomization: Patients identified by the Acute Stroke team as candidates for
      EVT will be referred to the study anesthesia team for consideration as study participants.
      Only after anesthetic pre-procedural assessment is complete, as per usual standard of care,
      and clinical uncertainty exists as to the best anesthetic management will the patient be
      randomized. Sequence generation: Randomization will be performed using REDCap to allow
      central randomization from any hospital computer with internet access. The blocked
      randomization sequence list will be created in STATA. The randomization instrument will be
      created in REDCap separate to the data collection tool to ensure blinding allocation is
      maintained. All treating consultant anesthetists will have access to the REDCap randomization
      instrument. User rights will be set so that these clinicians do not have access to
      participant follow-up data. Details of each procedure (GA or sedation) are outlined below.
      The attending anesthetist will log-on to REDCap and access the Randomization tool. This
      process will take 2-3 minutes once trained in the randomization process.

      Blinding: Both patient and treating physician will be aware of the treatment assignment.
      Post-procedural functional outcomes will be performed by a dedicated clinician blinded to the
      treatment assignment. Interventions: Physiological Parameters: Target Values (Talke et al.,
      2014) • Oxygenation: Maintain SpO2 > 92% and PaO2 > 60 mmHg. • Ventilation: Maintain
      normocapnia, PaCO2 35-45 mmHg under GA. Avoid respiratory-induced hypercarbia during sedation
      • Hemodynamics: Systolic blood pressure > 140 mmHg and < 180 mmHg. Diastolic blood pressure <
      105 mmHg. • Temperature: Maintain normothermia, T 35°C - 37°C. • Glucose control: Maintain
      blood glucose concentration 4.0 - 8.0 mmol/L. If blood glucose levels greater than 8 mmol/L
      (140 mg/dL) IV insulin infusion to be commenced. Blood glucose concentration to be repeated
      after 30 minutes. Hypoglycemia as defined by blood glucose < 3 mmol/L (50 mg/dL) should be
      treated with IV 10-20% glucose. General Anesthesia Protocol: (Melinda J. Davis, Cynthia R.
      Campos-Herrera, & David P. Archer, 2012; Powers et al., 2015; Talke et al., 2014) 1.
      Monitoring • American Society of Anesthesiologists (ASA) standard (non-invasive blood
      pressure (BP), electrocardiogram (ECG), oxygen saturation (SpO2), end-tidal carbon dioxide
      (ETCO2), temperature and neuromuscular monitoring (NMM)) • Invasive BP: direct measure of the
      arterial BP, with continuous pressure transduction and waveform display is the standard for
      blood pressure monitoring in AIS. It allows continuous BP assessment and provides reliable
      vascular access for frequent sampling. However, benefits of invasive arterial monitoring are
      null if the procedure itself delays reperfusion therapy (Saver, 2006). There is no consensus
      regarding timing of arterial access in EVT for AIS. This is our protocol: • 1 attempt with
      the patient awake • Maximum of 2 more attempts with the patient under anesthesia • Stop after
      a total of 3 attempts, or when the radiologist has access to the femoral artery. 2. Induction
      of anesthesia. 3. Neuromuscular paralysis. 4. Endotracheal intubation. 5. Positive pressure
      ventilation: ETCO2 range: 35-40 mmHg until arterial partial pressure of carbon dioxide
      (PaCO2) is obtained and the gap is measured. 6. Volatile anesthesia with sevoflurane or
      desflurane to a target age-compensated minimum alveolar concentration (MAC) > 0.5 but =
      1(Sivasankar et al., 2016) 7. Vasopressor support: If the systolic BP decreases more than 20%
      from pre-anesthetic value or is lower than 140 mmHg, the patient will receive vasopressor
      support as IV phenylephrine and/or ephedrine, titrated to effect. 8. Hypertension management:
      For systolic BP > 180 mmHg, IV labetalol will be administered, titrated to effect. 9.
      Arterial blood gas sampling to be performed at the earliest convenience after induction of
      anesthesia. Clinical goals are outlined above. 10. Temperature monitoring wit esophageal
      temperature probe. 11. Antagonism of neuromuscular blockade at the end of the procedure. The
      train of four should be = 0.9 prior to extubation (Hassan et al., 2012; Murphy GS, 2015). 12.
      Transfer the patient to the post-anesthesia care unit (PACU). Sedation Protocol: 1.
      Monitoring • ASA standard (non-invasive BP, ECG, SpO2, T, respiratory rate (RR), and ETCO2) •
      Invasive BP: a direct measure of the arterial blood pressure, • Maximum 3 attempts. Stop
      after a total of 3 attempts, or when the radiologist has access to the femoral artery. 2.
      Administer oxygen by nasal prongs or facial mask to achieve a target Sp02 = 92%. 3. Commence
      sedation: Remifentanil: 0.01-0.06 micrograms/kilogram/minute, titrated to effect. (Janssen et
      al., 2016) 4. Monitor RR. Decrease sedative infusion rate if RR < 6. 5. Vasopressor support:
      If the systolic BP decreases more than 20% from pre-anesthetic value or if is lower than 140
      mmHg, the patient will receive vasopressor support as IV phenylephrine and/or ephedrine,
      titrated to effect. 6. Hypertension management: For systolic BP > 180 mmHg, IV labetalol will
      be administered, titrated to effect. 7. Arterial blood gas sampling to be performed at the
      earliest convenience after induction of anesthesia. Clinical goals are outlined above. 8.
      Temperature monitoring with axillary temperature probe. 9. Transfer the patient to the PACU.

      Conversion of sedation to GA: Patients randomized to receive EVT under sedation will be
      converted to GA in cases of emergency (vascular injury), reduced level of consciousness
      (GCS<8), loss of airway reflexed, respiratory failure with rise in EtCO2 and agitation
      precluding safe conduct of EVT.

      Post-Procedural Follow-up:This will be conducted by a clinical research assistant who is
      blinded to the study intervention. The specifics of the follow-up procedure are detailed
      below: Day1: The NIHSS clinical scoring tool will be performed on the stoke inpatient unit.
      This scale is a validated tool to objectively quantify disability following a stroke. The
      tool entails assessment of level of consciousness, motor function, sensation, coordination,
      speech and concentration. Currently, this tool is utilised at LHSC as part of the follow-up
      for AIS post-procedural days 1. Day 1-2: All patients will have a CT angiogram and MRI within
      24-48 hours post-procedure as per usual standard of care. From these scans, the Thrombolysis
      in Cerebral Infarction (TICI) scale and final infarct volume will be calculated. Day 7: The
      NIHSS will be repeated to quantify ongoing disability. Day 90: As per the usual standard of
      care, all patient discharged from hospital will have a 3 month post-stroke outpatient
      follow-up appointment. The mRS and NIHSS will be repeated by the clinical research assistant
      at the neurological outpatient appointment. Should the appointment be delayed longer than 3
      months post-stroke, a telephone call will be made by the clinical research assistant to
      determine the mRS. If the patient remains an inpatient at 90 days post-stroke, the electronic
      record will be accessed to gain the required information to calculate the mRS
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: There will be two arms of this study. In the first arm, the patients who meet the inclusion criteria of the study will be randomized to receive general anesthesia during endovascular treatment for stroke. In the second arm of the study, patients will receive general sedation during endovascular treatment.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The outcomes assessor who will analyze the outcome variables for this study (consciousness, motor function, sensation, speech, coordination, standard of care follow up assessments etc.) that may be impacted by choice of anesthesia/analgesia will be blinded to the treatment group of the participants to ensure unbiased reporting.
measure: Randomization potential
time frame: 20 weeks
description: Total number of participants that have been recruited and the drop out rates. Recruitment goal is 20 patients within 20 weeks.
measure: Number of participants that complete the recruitment procedure prior to start of endovascular treatment.
time frame: 20 weeks
description: These procedures include patient identification and baseline assessments such as patient co-morbidities, demographics, and pre-procedural anesthetic assessment.
measure: Length of time to complete/completeness of study-related assessments
time frame: 1 year
description: To assess the feasibility of obtaining completed follow up assessments with this patient population and the time it takes to accomplish this.
arm group label: General Anesthesia
arm group type: Experimental
description: Patients who have had a stroke and meet the inclusion criteria for the study will receive general anesthesia during endovascular treatment. Choice of anesthetic for general anesthesia is dependent upon the patient condition and decision of the treating anesthesiologist (ketamine, propofol, fentanyl, midazolam,dexmedetomidine etc.). General Anesthesia Protocol: (Melinda J. Davis, Cynthia R. Campos-Herrera, & David P. Archer, 2012; Powers et al., 2015; Talke et al., 2014). Patient will be monitored in accordance with standard monitoring guidelines and the rest of the procedure will proceed in accordance with standard of care.
See Detailed Description for additional details and description of follow-up procedures.
arm group label: Conscious Sedation with Remifentanil
arm group type: Experimental
description: Patients who have had a stroke and meet the inclusion criteria for the study will receive conscious during endovascular treatment. Sedation will be accomplished using Remifentanil: 0.01-0.06 micrograms/kilogram/minute, titrated to effect. (Janssen et al., 2016). Patients who have had a stroke and meet the inclusion criteria for the study will receive general anesthesia during endovascular treatment. Patient will be monitored in accordance with standard monitoring guidelines and the rest of the procedure will proceed in accordance with standard of care.
See Detailed Description for additional details and description of follow-up procedures.
intervention type: Drug
intervention name: General Anesthesia
description: Patients who have had a stroke and meet the inclusion criteria for the study will receive general anesthesia during endovascular treatment. Choice of anesthetic for general anesthesia is dependent upon the patient condition and decision of the treating anesthesiologist (ketamine, propofol, fentanyl, midazolam,dexmedetomidine etc.). Induction of general anesthesia will follow standard treatment methods (Davis et al, 2012, Powers et al. 2015 Talke et al. 2015). Patient monitoring and care will proceed in accordance with standard of care guidelines. Refer to Detailed Description section for complete protocol information.
arm group label: General Anesthesia
other name: No other names
intervention type: Drug
intervention name: Conscious Sedation with Remifentanil
description: Patients who have had a stroke and meet the inclusion criteria for the study will receive conscious during endovascular treatment. Sedation will be accomplished using Remifentanil: 0.01-0.06 micrograms/kilogram/minute, titrated to effect. (Janssen et al., 2016). Patient monitoring and care will proceed in accordance with standard of care guidelines. Refer to Detailed Description section for complete protocol information.
arm group label: Conscious Sedation with Remifentanil
other name: No other names
criteria: 
gender: All
minimum age: 19 Years
maximum age: 95 Years
healthy volunteers: No
last name: Miguel Arango
role: Principal Investigator
affiliation: Lawson Health Research Institute
last name: Miguel Arango
phone: 519-685-8500
phone ext: 35571
email: miguel.arango@lhsc.on.ca
citation: Avitsian R, Machado SB. Anesthesia for Endovascular Approaches to Acute Ischemic Stroke. Anesthesiol Clin. 2016 Sep;34(3):497-509. doi: 10.1016/j.anclin.2016.04.004.
PMID: 27521194
citation: Brinjikji W, Murad MH, Rabinstein AA, Cloft HJ, Lanzino G, Kallmes DF. Conscious sedation versus general anesthesia during endovascular acute ischemic stroke treatment: a systematic review and meta-analysis. AJNR Am J Neuroradiol. 2015 Mar;36(3):525-9. doi: 10.3174/ajnr.A4159. Epub 2014 Nov 13.
PMID: 25395655
citation: Dhakal LP, Diaz-Gomez JL, Freeman WD. Role of anesthesia for endovascular treatment of ischemic stroke: do we need neurophysiological monitoring? Stroke. 2015 Jun;46(6):1748-54. doi: 10.1161/STROKEAHA.115.008223. Epub 2015 May 7. No abstract available.
PMID: 25953376
citation: Davis MJ, Menon BK, Baghirzada LB, Campos-Herrera CR, Goyal M, Hill MD, Archer DP; Calgary Stroke Program. Anesthetic management and outcome in patients during endovascular therapy for acute stroke. Anesthesiology. 2012 Feb;116(2):396-405. doi: 10.1097/ALN.0b013e318242a5d2.
PMID: 22222475
citation: Talke PO, Sharma D, Heyer EJ, Bergese SD, Blackham KA, Stevens RD. Republished: Society for Neuroscience in Anesthesiology and Critical Care expert consensus statement: Anesthetic management of endovascular treatment for acute ischemic stroke. Stroke. 2014 Aug;45(8):e138-50. doi: 10.1161/STROKEAHA.113.003412.
PMID: 25070964
citation: Janssen H, Buchholz G, Killer M, Ertl L, Bruckmann H, Lutz J. General Anesthesia Versus Conscious Sedation in Acute Stroke Treatment: The Importance of Head Immobilization. Cardiovasc Intervent Radiol. 2016 Sep;39(9):1239-44. doi: 10.1007/s00270-016-1411-5. Epub 2016 Jul 7.
PMID: 27387186
citation: Sivasankar C, Stiefel M, Miano TA, Kositratna G, Yandrawatthana S, Hurst R, Kofke WA. Anesthetic variation and potential impact of anesthetics used during endovascular management of acute ischemic stroke. J Neurointerv Surg. 2016 Nov;8(11):1101-1106. doi: 10.1136/neurintsurg-2015-011998. Epub 2015 Nov 27.
PMID: 26614493
responsible party type: Principal Investigator
investigator affiliation: Lawson Health Research Institute
investigator full name: Miguel Arango
investigator title: Anesthesiologist, Associate Professor
mesh term: Stroke
mesh term: Remifentanil
sharing ipd: No