<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/NCT02976584</url>
  </required_header>
  <id_info>
    <org_study_id>KEK210/15</org_study_id>
    <nct_id>NCT02976584</nct_id>
  </id_info>
  <brief_title>Epileptic Potentials During Cardiac Surgery and Association With Postoperative Neurological Outcome</brief_title>
  <acronym>EPOCAS</acronym>
  <official_title>Incidence of Epileptic Potentials During Cardiac Surgery and Postoperative Neurological Outcome: A Prospective Observational Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heiko Kaiser</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primarily, the investigators want to test the hypothesis that it is possible to detect&#xD;
      epileptiform EEG during cardiac surgery under general anesthesia.&#xD;
&#xD;
      Furthermore, the investigators will examine if those epileptic potentials coincide, follow or&#xD;
      are unrelated to ischemic events detected by EEG or Near-infrared spectroscopy (NIRS).&#xD;
      Finally, the investigators will look for independent associations between intraoperative&#xD;
      seizures (with or without ischemic events) and postoperative neurological outcome, as well as&#xD;
      between intraoperative seizures (with or without ischemic events) and the total amount of TXA&#xD;
      given.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will follow the STROBE guidelines to perform this prospective observational&#xD;
      study. All patient demographics, co-morbidities and surgical details that are relevant to&#xD;
      calculate the EuroSCORE will be recorded using our institutional automatic anesthesia record&#xD;
      system. Laboratory tests will be performed according to our clinical standard before cardiac&#xD;
      surgery. General anesthesia and surgery will be performed according to attending physician's&#xD;
      preferences. Invasive arterial blood pressure, central line and transesophageal&#xD;
      echocardiography (TEE) are all standard procedures. Before induction of anesthesia a two&#xD;
      channel EEG will be installed on the forehead with reference electrode on FPZ, other&#xD;
      electrodes on A1-F3 &amp; A2-F4. A Narcotrend Compact M Monitor will be connected to evaluate&#xD;
      depth of anesthesia continuously during the operation, but also automatically stores EEG data&#xD;
      (with a rate of 128Hz) to screen for epileptic activity or/and ischemic episodes. This&#xD;
      monitor is standard practice in our cardiovascular division.&#xD;
&#xD;
      Patients at higher risk for intraoperative cerebral ischemic events (stenosis of carotid&#xD;
      artery, deep hypothermic cardiac arrest, history of stroke/prind/TIA, severe aortic&#xD;
      atherosclerotic disease) do receive bilateral frontal brain oxygenation/perfusion monitoring&#xD;
      with Near-infrared spectroscopy (NIRS) as part of standard practice at our institution. After&#xD;
      the administration of the anticoagulant heparin for cardiopulmonary bypass, tranexamic acid&#xD;
      is given intravenously as our clinical standard according to the BART trial. All other&#xD;
      intraoperative administrations of drugs, blood transfusions and hemodynamic management will&#xD;
      be according to the responsible cardiac anesthesiologist and cardiac surgeon. Following&#xD;
      surgery patients will be transported to the ICU under deep sedation according to the&#xD;
      anesthesia team. As standard operation procedure the responsible ICU attending or resident is&#xD;
      evaluating cardiac surgery patients every hours while intubated and at least twice per shift&#xD;
      if awake (4 times per day) for neurological deficits. A neurological deficit is defined as&#xD;
      patient developing a new onset motor, sensory, or cognitive dysfunction (e.g., hemiplegia,&#xD;
      hemiparesis, aphasia, sensory deficit, impaired memory) that persists for 24 or more hours&#xD;
      due to embolic, thrombotic, or hemorrhagic vascular accident or stroke. Special trained ICU&#xD;
      nurses evaluate the Richmond Agitation Sedation Scale (RASS) on an hourly basis. The time&#xD;
      from stopping sedation until reaching a RASS of zero will be used to determine (delayed) time&#xD;
      to awakening. The appropriateness of timing to stop the sedation is up to the treating ICU&#xD;
      team.&#xD;
&#xD;
      Standard practice is, that cardiac enzymes are measured all 6 hours for the first 48 hours,&#xD;
      according to clinical judgement thereafter, but at least once daily until discharge from the&#xD;
      ICU. New myocardial infarction will be defined as Troponin values &gt;10x99th percentile URL&#xD;
      during the first 48 h following cardiac surgery, occurring from a normal baseline Troponin&#xD;
      value (≤99th percentile URL). In addition, either (i) new pathological Q waves or new LBBB,&#xD;
      or (ii) angiographically documented new graft or new native coronary artery occlusion, or&#xD;
      (iii) imaging evidence of new loss of viable myocardium or new regional wall motion&#xD;
      abnormality.&#xD;
&#xD;
      Pulmonary and respiratory complications will be noted as (1) pneumonia, (2) prolonged&#xD;
      intubation of &gt; 24 hours, (3) re-intubation, (4) TRALI or ARDS, as well as (5) tracheostomy&#xD;
      due to weaning failure.&#xD;
&#xD;
      Renal complication is defined as acute renal failure (ARF) requiring dialysis during the&#xD;
      postoperative period. The indication for dialysis include uremia, volume overload, or&#xD;
      biochemical abnormalities and are based on clinical judgment of the treating ICU team.&#xD;
&#xD;
      The exact time on the ICU and on the ventilator is automatically recorded in the patient data&#xD;
      management system (PDMS) and will be recorded on the day of ICU discharge and/or extubation.&#xD;
      All postoperative diagnosis of complications will be gathered from the involved intensivist,&#xD;
      cardiac surgeon, cardiologist, neurologist, radiologist and other consulted specialists.&#xD;
      Mortality will be evaluated for in hospital only.&#xD;
&#xD;
      The postoperative course of all included patients will be followed until discharge from the&#xD;
      hospital.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 11, 2016</start_date>
  <completion_date type="Actual">January 2018</completion_date>
  <primary_completion_date type="Actual">November 24, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of intraoperative epileptic seizures</measure>
    <time_frame>Up to 1 day</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neurologic injury (Stroke, PRIND, TIA)</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delayed wakening from anesthesia</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative cardiac/pulmonary/renal complications</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time on the ventilator</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">1067</enrollment>
  <condition>Epilepsy</condition>
  <condition>Cardiac Disease</condition>
  <condition>Peroperative Complications</condition>
  <condition>Anesthesia; Adverse Effect</condition>
  <condition>Ischemia, Cerebral</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Patients that are undergoing elective or emergent cardiac or major aortic surgery with&#xD;
        cardiopulmonary bypass and are at least 18 years old.&#xD;
&#xD;
        Single-centre: INSELSPITAL, Bern, Switzerland&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients that are undergoing elective or emergent cardiac or major aortic surgery with&#xD;
             cardiopulmonary bypass.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients refusing to consent to our institutional protected health information policy&#xD;
             on the consent document for anesthesia or the general consent of the INSELSPITAL.&#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>Heiko Kaiser, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dept. of Anesthesiology and Pain Therapy, Division of Cardiovascular Anesthesia, University Hospital Inselspital, Berne</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Inselspital</name>
      <address>
        <city>Berne</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <link>
    <url>http://www.admin.ch/opc/en/classified-compilation/20121177/index.html</url>
    <description>Ordinance on Human Research with the Exception of Clinical Trials (Human Research Ordinance, HRO)</description>
  </link>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 19, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>May 22, 2018</last_update_submitted>
  <last_update_submitted_qc>May 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Insel Gruppe AG, University Hospital Bern</investigator_affiliation>
    <investigator_full_name>Heiko Kaiser</investigator_full_name>
    <investigator_title>Dr. med.</investigator_title>
  </responsible_party>
  <keyword>EEG</keyword>
  <keyword>Cardiac Surgery</keyword>
  <keyword>Seizure</keyword>
  <keyword>Tranexamic acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Intraoperative Complications</mesh_term>
  </condition_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/NCT02976584
org study id: KEK210/15
nct id: NCT02976584
lead sponsor: 
has dmc: No
Primarily, the investigators want to test the hypothesis that it is possible to detect
      epileptiform EEG during cardiac surgery under general anesthesia.

      Furthermore, the investigators will examine if those epileptic potentials coincide, follow or
      are unrelated to ischemic events detected by EEG or Near-infrared spectroscopy (NIRS).
      Finally, the investigators will look for independent associations between intraoperative
      seizures (with or without ischemic events) and postoperative neurological outcome, as well as
      between intraoperative seizures (with or without ischemic events) and the total amount of TXA
      given.
The investigators will follow the STROBE guidelines to perform this prospective observational
      study. All patient demographics, co-morbidities and surgical details that are relevant to
      calculate the EuroSCORE will be recorded using our institutional automatic anesthesia record
      system. Laboratory tests will be performed according to our clinical standard before cardiac
      surgery. General anesthesia and surgery will be performed according to attending physician's
      preferences. Invasive arterial blood pressure, central line and transesophageal
      echocardiography (TEE) are all standard procedures. Before induction of anesthesia a two
      channel EEG will be installed on the forehead with reference electrode on FPZ, other
      electrodes on A1-F3 & A2-F4. A Narcotrend Compact M Monitor will be connected to evaluate
      depth of anesthesia continuously during the operation, but also automatically stores EEG data
      (with a rate of 128Hz) to screen for epileptic activity or/and ischemic episodes. This
      monitor is standard practice in our cardiovascular division.

      Patients at higher risk for intraoperative cerebral ischemic events (stenosis of carotid
      artery, deep hypothermic cardiac arrest, history of stroke/prind/TIA, severe aortic
      atherosclerotic disease) do receive bilateral frontal brain oxygenation/perfusion monitoring
      with Near-infrared spectroscopy (NIRS) as part of standard practice at our institution. After
      the administration of the anticoagulant heparin for cardiopulmonary bypass, tranexamic acid
      is given intravenously as our clinical standard according to the BART trial. All other
      intraoperative administrations of drugs, blood transfusions and hemodynamic management will
      be according to the responsible cardiac anesthesiologist and cardiac surgeon. Following
      surgery patients will be transported to the ICU under deep sedation according to the
      anesthesia team. As standard operation procedure the responsible ICU attending or resident is
      evaluating cardiac surgery patients every hours while intubated and at least twice per shift
      if awake (4 times per day) for neurological deficits. A neurological deficit is defined as
      patient developing a new onset motor, sensory, or cognitive dysfunction (e.g., hemiplegia,
      hemiparesis, aphasia, sensory deficit, impaired memory) that persists for 24 or more hours
      due to embolic, thrombotic, or hemorrhagic vascular accident or stroke. Special trained ICU
      nurses evaluate the Richmond Agitation Sedation Scale (RASS) on an hourly basis. The time
      from stopping sedation until reaching a RASS of zero will be used to determine (delayed) time
      to awakening. The appropriateness of timing to stop the sedation is up to the treating ICU
      team.

      Standard practice is, that cardiac enzymes are measured all 6 hours for the first 48 hours,
      according to clinical judgement thereafter, but at least once daily until discharge from the
      ICU. New myocardial infarction will be defined as Troponin values >10x99th percentile URL
      during the first 48 h following cardiac surgery, occurring from a normal baseline Troponin
      value (≤99th percentile URL). In addition, either (i) new pathological Q waves or new LBBB,
      or (ii) angiographically documented new graft or new native coronary artery occlusion, or
      (iii) imaging evidence of new loss of viable myocardium or new regional wall motion
      abnormality.

      Pulmonary and respiratory complications will be noted as (1) pneumonia, (2) prolonged
      intubation of > 24 hours, (3) re-intubation, (4) TRALI or ARDS, as well as (5) tracheostomy
      due to weaning failure.

      Renal complication is defined as acute renal failure (ARF) requiring dialysis during the
      postoperative period. The indication for dialysis include uremia, volume overload, or
      biochemical abnormalities and are based on clinical judgment of the treating ICU team.

      The exact time on the ICU and on the ventilator is automatically recorded in the patient data
      management system (PDMS) and will be recorded on the day of ICU discharge and/or extubation.
      All postoperative diagnosis of complications will be gathered from the involved intensivist,
      cardiac surgeon, cardiologist, neurologist, radiologist and other consulted specialists.
      Mortality will be evaluated for in hospital only.

      The postoperative course of all included patients will be followed until discharge from the
      hospital.
observational model: Case-Only
time perspective: Prospective
measure: Incidence of intraoperative epileptic seizures
time frame: Up to 1 day
measure: Neurologic injury (Stroke, PRIND, TIA)
time frame: up to 30 days
measure: Delayed wakening from anesthesia
time frame: up to 30 days
measure: Postoperative cardiac/pulmonary/renal complications
time frame: up to 30 days
measure: Mortality
time frame: up to 30 days
measure: Time on the ventilator
time frame: up to 30 days
measure: ICU length of stay
time frame: up to 30 days
measure: Hospital length of stay
time frame: up to 30 days
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Heiko Kaiser, MD
role: Principal Investigator
affiliation: Dept. of Anesthesiology and Pain Therapy, Division of Cardiovascular Anesthesia, University Hospital Inselspital, Berne
facility: 
country: Switzerland
url: http://www.admin.ch/opc/en/classified-compilation/20121177/index.html
description: Ordinance on Human Research with the Exception of Clinical Trials (Human Research Ordinance, HRO)
responsible party type: Sponsor-Investigator
investigator affiliation: Insel Gruppe AG, University Hospital Bern
investigator full name: Heiko Kaiser
investigator title: Dr. med.
mesh term: Brain Ischemia
mesh term: Heart Diseases
mesh term: Ischemia
mesh term: Intraoperative Complications
sharing ipd: No