<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/NCT03032471</url>
  </required_header>
  <id_info>
    <org_study_id>2017_MST_01</org_study_id>
    <nct_id>NCT03032471</nct_id>
  </id_info>
  <brief_title>Swiss SOS MoCA - DCI Study</brief_title>
  <official_title>Impact of Delayed Cerebral Ischemia (DCI) on the Neuropsychological Outcome After Aneurysmal Subarachnoid Hemorrhage - a SWISS SOS Multicentre Observational Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Swiss SOS Study Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universitätsklinik für Neurochirurgie, Inselspital Bern</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Département des Neurosciences cliniques, Service de Neurochirurgie, Hôpitaux Universitaires de Genève</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Primario Neurochirurgia, EOC Ospedale Regionale di Lugano - Civico e Italiano</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Klinik für Neurochirurgie, Kantonsspital St. Gallen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Klinik für Neurochirurgie, Universitätsspital Zürich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Abteilung für Neuropsychologie, Universitätsklinik für Neurologie, Inselspital Bern</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Primario Neurologia, EOC Ospedale Regionale di Lugano - Civico e Italiano</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Abteilung für Neuropsychologie, Klinik für Neurologie, Kantonsspital St.Gallen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Abteilung für Neuropsychologie, Klinik für Neurologie, Universitätsspital Zürich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Département des Neurosciences cliniques, Service de Neurochirurgie, CHUV, Lausanne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Département des Neurosciences cliniques, Service de Neurologie, CHUV, Lausanne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Département des Neurosciences cliniques, Service de Neurologie, Hôpitaux Universitaires de Genève</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Swiss SOS Study Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this multicenter observational study is to determine the effect size&#xD;
      of the relationship between DCI and neuropsychological impairment 14-28 days and 3 months&#xD;
      after aSAH.&#xD;
&#xD;
      Secondary objectives are the feasibility to administer and the validity of the MoCA in an&#xD;
      intensive care unit setting, as well as the test/retest reliability of the MoCA in patients&#xD;
      with acute brain damage in absence of aSAH.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background and rationale:&#xD;
&#xD;
      Delayed cerebral ischemia (DCI) is the independent most important predictor of neurological&#xD;
      disability in survivors following aneurysmal subarachnoid hemorrhage (aSAH). DCI could also&#xD;
      be identified as the most important predictor of moderate to severe neuropsychological&#xD;
      impairment following aSAH. Only few prospective studies so far specifically analyzed the&#xD;
      effect size of the relationship between DCI and neuropsychological impairment, and all&#xD;
      studies had a methodological weakness: lack of a baseline neuropsychological assessment&#xD;
      before the onset of DCI.&#xD;
&#xD;
      In studies analyzing the neuropsychological outcome after aSAH, the Montreal Cognitive&#xD;
      Assessment (MoCA) is the most comprehensive, sensitive and specific instrument among the&#xD;
      short tests. The MoCA is increasingly used in the aSAH population, while its validity and&#xD;
      reliability has only been demonstrated in the normal population or patients suffering from&#xD;
      diseases different from aSAH, such as e.g. Parkinson's disease or dementia. Today,&#xD;
      neuropsychological examinations find entry into clinical routine for aSAH patients to&#xD;
      estimate the need for inpatient rehabilitation. However, the MoCA is often applied to aSAH&#xD;
      patients in a busy intensive or intermediate care unit, while it remains largely unknown&#xD;
      whether the distraction in such an environment represents a bias to the obtained results.&#xD;
&#xD;
      This study therefore evaluates aSAH patients before and after the phase of DCI, as well as&#xD;
      three months after aSAH, in order to estimate the impact of DCI on neuropsychological&#xD;
      impairment. In addition, the extent and location of cerebral ischemia, as measured with the&#xD;
      Alberta Stroke Program Early CT Score (ASPECTS) is correlated with the neuropsychological&#xD;
      outcome.&#xD;
&#xD;
      Furthermore, the study measures the test/retest reliability of the MoCA, as well as the&#xD;
      influence of the intensive care environment on the MoCA results in a randomized fashion in&#xD;
      subjects with acute brain damage (and no aSAH).&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      The primary objective of this multicenter observational study is to determine the effect size&#xD;
      of the relationship between DCI and neuropsychological impairment 14-28 days and 3 months&#xD;
      after aSAH.&#xD;
&#xD;
      Secondary objectives are the feasibility to administer and the validity of the MoCA in an&#xD;
      intensive care unit setting, as well as the test/retest reliability of the MoCA in patients&#xD;
      with acute brain damage in absence of aSAH.&#xD;
&#xD;
      Outcomes:&#xD;
&#xD;
      The primary endpoint is the proportion of patients with or without DCI that show worsening on&#xD;
      the MoCA 3 months after the ictus as compared to before the DCI phase by at least two points.&#xD;
&#xD;
      Key secondary endpoints for part 1 of the study are:&#xD;
&#xD;
        -  The proportion of patients with or without DCI that show worsening on the MoCA 14-28&#xD;
           days after the ictus as compared to before the DCI phase by at least two points.&#xD;
&#xD;
        -  The absolute difference of the MoCA before and after the active phase of DCI in patients&#xD;
           with versus without DCI.&#xD;
&#xD;
        -  The absolute difference of the MoCA before the active phase of DCI and 3 months after&#xD;
           aSAH in patients with versus without DCI&#xD;
&#xD;
        -  The rate of patients with versus without DCI that show cognitive impairment at 14-28&#xD;
           days and 3 months (defined as MoCA &lt; 26 points)&#xD;
&#xD;
        -  The correlation of neuropsychological outcome with the extent and location of ischemic&#xD;
           lesions on brain CT-scan 12-21 days post-SAH, graded by the semi-quantitative&#xD;
           ASPECT-grading&#xD;
&#xD;
        -  Health-related quality of life at 3 months in patients with versus without DCI&#xD;
&#xD;
        -  Home-time at 3 months in patients with versus without DCI&#xD;
&#xD;
        -  Death and dependency at 3 months in patients with versus without DCI&#xD;
&#xD;
        -  The absolute MoCA result, health-related quality of life and home-time at 3 months in&#xD;
           patients with versus without hydrocephalus requiring shunting&#xD;
&#xD;
        -  The absolute MoCA result, health-related quality of life and home-time at 3 months in&#xD;
           patients with surgical versus endovascular aneurysm occlusion&#xD;
&#xD;
      Key secondary endpoints for part 2 of the study are:&#xD;
&#xD;
        -  The test/retest reliability of the MoCA in patients with acute brain damage&#xD;
&#xD;
        -  The influence of the intensive care environment on the MoCA in patients with acute brain&#xD;
           damage&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    COVID-restrictions on clinical research in Switzerland&#xD;
  </why_stopped>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Actual">May 6, 2022</completion_date>
  <primary_completion_date type="Actual">May 6, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Neuropsychological deterioration on the MoCA</measure>
    <time_frame>3 months after Subarachnoid Hemorrhage</time_frame>
    <description>The primary endpoint is the in-subject difference of the MoCA before (48-72h after aSAH) and after the active phase of DCI (3 months after aSAH) between patients with and without DCI. The MoCA scores will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neuropsychological deterioration on the MoCA</measure>
    <time_frame>Up to 28 days after Subarachnoid Hemorrhage (directly after the DCI phase)</time_frame>
    <description>As for the primary outcome, the MoCA at 14-28 days after aSAH will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychological outcome</measure>
    <time_frame>Up to 3 months after Subarachnoid Hemorrhage</time_frame>
    <description>Absolute results of the MoCA at 48-72h, 14-28 days and 3 months in patients that develop and those that do not develop DCI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reliability of the MoCA in patients with acute brain injury</measure>
    <time_frame>Up to 1 month following acute brain injury</time_frame>
    <description>Reliability of the MoCA when tested in a (busy) intermediate care (IMC)/intensive care unit (ICU), as compared to the testing in a (quiet) setting in patients with acute brain injury.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Test-retest reliability of the MoCA in patients with acute brain injury</measure>
    <time_frame>Up to 1 month following acute brain injury</time_frame>
    <description>Test-retest reliability of the MoCA in patients with acute brain injury, tested two consecutive times with the MoCA (within 36 hours).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between MoCA and CT-imaging</measure>
    <time_frame>Up to 72 hours after Subarachnoid Hemorrhage</time_frame>
    <description>Correlation of the MoCA at 48-72h with the ASPECTS score for ischemic lesions on the CT-scan at 24-72h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between MoCA and CT-imaging</measure>
    <time_frame>Up to 28 days after Subarachnoid Hemorrhage (directly after the DCI phase)</time_frame>
    <description>Correlation of the MoCA at 14-28 days with the ASPECTS score for ischemic lesions on the CT-scan at 12-21 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between MoCA and CT-imaging</measure>
    <time_frame>3 months after Subarachnoid Hemorrhage</time_frame>
    <description>Correlation of the MoCA at 3 months with the ASPECTS score for ischemic lesions on the CT-scan between 6 weeks and 3 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dependency/Mortality</measure>
    <time_frame>3 months after Subarachnoid Hemorrhage</time_frame>
    <description>Will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI) based on the mRS at 3 months, where modified Rankin Scale (mRS) 4 and 5 is considered as dependency, and mRS 6 is considered dead</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life (HRQoL)</measure>
    <time_frame>3 months after Subarachnoid Hemorrhage</time_frame>
    <description>Will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI) using the Euro-Qol (EQ-5D)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Shunt dependency (ventriculo-peritoneal or ventriculo-atrial shunt)</measure>
    <time_frame>3 months after Subarachnoid Hemorrhage</time_frame>
    <description>Will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Home time</measure>
    <time_frame>3 months after Subarachnoid Hemorrhage</time_frame>
    <description>Length of time (in days) spent in own home or relative's home since Subarachnoid Hemorrhage. Will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Clinically Important Difference (MCID) of the MoCA</measure>
    <time_frame>Up to 3 months after Subarachnoid Hemorrhage</time_frame>
    <description>The MCID in patients with aneurysmal Subarachnoid Hemorrhage is determined using three different anchor-based approaches (using the GCS and NIHSS as anchors), namely the average change approach, minimum detectable change approach, and the change difference approach.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Random number generation</measure>
    <time_frame>Up to 1 month following acute brain injury</time_frame>
    <description>Random number generation, as a test of frontal executive functions in patients with acute brain injury will be assessed using the mental dice task by a neuropsychologist not involved in the treatment of the patient.</description>
  </other_outcome>
  <other_outcome>
    <measure>Outcomes in patients with hydrocephalus vs. without hydrocephalus</measure>
    <time_frame>Up to 3 months after Subarachnoid Hemorrhage</time_frame>
    <description>Outcomes 1, 2, 3 and 9-12 will be compared between patients that develop or do not develop hydrocephalus up to 3 months after Subarachnoid Hemorrhage.</description>
  </other_outcome>
  <other_outcome>
    <measure>Outcomes in patiens treated surgically vs. endovascularly (aneurysm occlusion)</measure>
    <time_frame>Up to 3 months after Subarachnoid Hemorrhage</time_frame>
    <description>Outcomes 1, 2, 3 and 9-12 will be compared between patients that are treated surgically or endovascularly up to 3 months after Subarachnoid Hemorrhage.</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">128</enrollment>
  <condition>Subarachnoid Hemorrhage</condition>
  <condition>Delayed Cerebral Ischemia</condition>
  <condition>Stroke</condition>
  <condition>Complication</condition>
  <condition>Cognitive Impairment</condition>
  <condition>Cognitive Deficit</condition>
  <condition>Cognitive Deterioration</condition>
  <condition>Cognitive Deficits Following Cerebral Infarction</condition>
  <arm_group>
    <arm_group_label>DCI group</arm_group_label>
    <description>Patients that experience DCI, defined as&#xD;
Cerebral infarction identified on imaging or proven at autopsy, after exclusion of procedure-related infarctions; and&#xD;
Clinical deterioration caused by DCI, after exclusion of other potential causes of clinical deterioration will be assigned to the DCI group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-DCI group</arm_group_label>
    <description>Patients not experiencing DCI as defined above.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>There is no intervention for this study. Patients are allocated to the study groups based on whether or not DCI occurs.</intervention_name>
    <description>There is no intervention for this study. Patients are allocated to the study groups based on whether or not DCI occurs.</description>
    <arm_group_label>DCI group</arm_group_label>
    <arm_group_label>non-DCI group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        For part 1 of the study, patients with aneurysmal subarachnoid hemorrhage are recruited.&#xD;
&#xD;
        For part 2 of the study, patients with acute brain injury are recruited.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For part 1 of the study:&#xD;
&#xD;
        Participants fulfilling all of the following inclusion criteria are eligible for the study:&#xD;
&#xD;
          -  Consent of the patient or consent of patient's next of kin (plus consent of an&#xD;
             independent physician if patient is unable to consent)&#xD;
&#xD;
          -  Aneurysmal SAH&#xD;
&#xD;
          -  Age: ≥18&#xD;
&#xD;
          -  Time of aSAH known (IMPORTANT: at least approximated. Time of aSAH refers to the bleed&#xD;
             that lead to hospital admission; warning leaks in the patient history are not&#xD;
             considered aSAH in this context)&#xD;
&#xD;
          -  Complete aneurysm occlusion therapy within 48h after aSAH&#xD;
&#xD;
          -  Glasgow coma scale (GCS) ≥ 13 points at time point 48h - 72h after aSAH&#xD;
&#xD;
          -  Fluent language skills in either English, German, French, or Italian&#xD;
&#xD;
        For part 2 of the study:&#xD;
&#xD;
        Participants fulfilling all of the following inclusion criteria are eligible for the study:&#xD;
&#xD;
          -  Consent of the patient or consent of patient's next of kin (plus consent of an&#xD;
             independent physician if patient is unable to consent)&#xD;
&#xD;
          -  Age: ≥18&#xD;
&#xD;
          -  Acute brain injury that requires a in-patient treatment, e.g. for (surgical) treatment&#xD;
             of a brain tumor, a cerebral hemorrhage, a hydrocephalus, stroke, or traumatic brain&#xD;
             injury, with stable neurological and general health status&#xD;
&#xD;
          -  Glasgow coma scale (GCS) ≥ 13 points&#xD;
&#xD;
          -  Fluent language skills in either English, German, French, or Italian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For part 1 of the study:&#xD;
&#xD;
        The presence of any one of the following exclusion criteria will lead to exclusion of the&#xD;
        participant:&#xD;
&#xD;
          -  SAH due to any other cause than aneurysm or structural abnormality of the brain&#xD;
             (arterio-venous malformation, dural arterio-venous fistula, cavernous malformation,&#xD;
             dissection, tumor, trauma)&#xD;
&#xD;
          -  Comatose patients or patients with a reduced vigilance of GCS &lt; 13 at time point 48h -&#xD;
             72h after aSAH&#xD;
&#xD;
          -  No aneurysm occlusion therapy within 48h after aSAH&#xD;
&#xD;
          -  Clear signs of arterial vasospasm in the initial (CT-)angiography; indicating that&#xD;
             aSAH had occurred already several days prior to admission&#xD;
&#xD;
          -  Neurologic or psychiatric diseases other than aSAH that can potentially influence the&#xD;
             test-performance of a patient on the MoCA (e.g., dementia, multiple sclerosis, bipolar&#xD;
             disorder)&#xD;
&#xD;
          -  Foreseeable difficulties in follow-up due to geographic reasons (e.g., patients living&#xD;
             abroad)&#xD;
&#xD;
          -  Patients who are not fluent in English, German, French, or Italian&#xD;
&#xD;
          -  Patients requiring sedative or other medication that would interfere with the&#xD;
             neuropsychological evaluation&#xD;
&#xD;
        For part 2 of the study:&#xD;
&#xD;
        The presence of any one of the following exclusion criteria will lead to exclusion of the&#xD;
        participant:&#xD;
&#xD;
          -  Instable neurological or general health-status of the patient, that makes a transport&#xD;
             of the patient on the ICU or the office for neuropsychological testing impossible&#xD;
&#xD;
          -  Suspected fluctuation of the neurological condition and the vigilance of the patient&#xD;
             between first and second testing&#xD;
&#xD;
          -  Known psychiatric disease that can potentially influence the test-performance on the&#xD;
             MoCA (e.g., dementia, bipolar disorder)&#xD;
&#xD;
          -  Patients who are not fluent in English, German, French, or Italian&#xD;
&#xD;
          -  Patients requiring sedative or other medication that would interfere with the&#xD;
             neuropsychological evaluation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Primario Neurochirurgia, EOC Ospedale Regionale di Lugano - Civico e Italiano</name>
      <address>
        <city>Lugano</city>
        <state>Ticino</state>
        <zip>6900</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Vaudois (CHUV)</name>
      <address>
        <city>Lausanne</city>
        <state>Vaud</state>
        <zip>1011</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik für Neurochirurgie, Inselspital Bern</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Département des Neurosciences cliniques, Service de Neurochirurgie, Hôpitaux Universitaires de Genève</name>
      <address>
        <city>Genève</city>
        <zip>1211</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik für Neurochirurgie, Kantonsspital St. Gallen</name>
      <address>
        <city>St.Gallen</city>
        <zip>9007</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik für Neurochirurgie, Universitätsspital Zürich</name>
      <address>
        <city>Zürich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>May 6, 2022</last_update_submitted>
  <last_update_submitted_qc>May 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Subarachnoid Hemorrhage</keyword>
  <keyword>Delayed cerebral ischemia</keyword>
  <keyword>Cognitive Impairment</keyword>
  <keyword>Montreal Cognitive Assessment</keyword>
  <keyword>MoCA</keyword>
  <keyword>Cognitive Deterioration</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Subarachnoid Hemorrhage</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Infarction</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
    <mesh_term>Cognition Disorders</mesh_term>
  </condition_browse>
  <study_docs>
    <study_doc>
      <doc_type>Study Protocol</doc_type>
      <doc_url>http://swiss-sos.ch/study/2_SYNOPSIS.pdf</doc_url>
      <doc_comment>Study synopsis; for the complete protocol please request from Martin N. Stienen</doc_comment>
    </study_doc>
  </study_docs>
  <!-- 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/NCT03032471
org study id: 2017_MST_01
nct id: NCT03032471
lead sponsor: 
collaborator: 
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has dmc: Yes
The primary objective of this multicenter observational study is to determine the effect size
      of the relationship between DCI and neuropsychological impairment 14-28 days and 3 months
      after aSAH.

      Secondary objectives are the feasibility to administer and the validity of the MoCA in an
      intensive care unit setting, as well as the test/retest reliability of the MoCA in patients
      with acute brain damage in absence of aSAH.
Background and rationale:

      Delayed cerebral ischemia (DCI) is the independent most important predictor of neurological
      disability in survivors following aneurysmal subarachnoid hemorrhage (aSAH). DCI could also
      be identified as the most important predictor of moderate to severe neuropsychological
      impairment following aSAH. Only few prospective studies so far specifically analyzed the
      effect size of the relationship between DCI and neuropsychological impairment, and all
      studies had a methodological weakness: lack of a baseline neuropsychological assessment
      before the onset of DCI.

      In studies analyzing the neuropsychological outcome after aSAH, the Montreal Cognitive
      Assessment (MoCA) is the most comprehensive, sensitive and specific instrument among the
      short tests. The MoCA is increasingly used in the aSAH population, while its validity and
      reliability has only been demonstrated in the normal population or patients suffering from
      diseases different from aSAH, such as e.g. Parkinson's disease or dementia. Today,
      neuropsychological examinations find entry into clinical routine for aSAH patients to
      estimate the need for inpatient rehabilitation. However, the MoCA is often applied to aSAH
      patients in a busy intensive or intermediate care unit, while it remains largely unknown
      whether the distraction in such an environment represents a bias to the obtained results.

      This study therefore evaluates aSAH patients before and after the phase of DCI, as well as
      three months after aSAH, in order to estimate the impact of DCI on neuropsychological
      impairment. In addition, the extent and location of cerebral ischemia, as measured with the
      Alberta Stroke Program Early CT Score (ASPECTS) is correlated with the neuropsychological
      outcome.

      Furthermore, the study measures the test/retest reliability of the MoCA, as well as the
      influence of the intensive care environment on the MoCA results in a randomized fashion in
      subjects with acute brain damage (and no aSAH).

      Objectives:

      The primary objective of this multicenter observational study is to determine the effect size
      of the relationship between DCI and neuropsychological impairment 14-28 days and 3 months
      after aSAH.

      Secondary objectives are the feasibility to administer and the validity of the MoCA in an
      intensive care unit setting, as well as the test/retest reliability of the MoCA in patients
      with acute brain damage in absence of aSAH.

      Outcomes:

      The primary endpoint is the proportion of patients with or without DCI that show worsening on
      the MoCA 3 months after the ictus as compared to before the DCI phase by at least two points.

      Key secondary endpoints for part 1 of the study are:

        -  The proportion of patients with or without DCI that show worsening on the MoCA 14-28
           days after the ictus as compared to before the DCI phase by at least two points.

        -  The absolute difference of the MoCA before and after the active phase of DCI in patients
           with versus without DCI.

        -  The absolute difference of the MoCA before the active phase of DCI and 3 months after
           aSAH in patients with versus without DCI

        -  The rate of patients with versus without DCI that show cognitive impairment at 14-28
           days and 3 months (defined as MoCA < 26 points)

        -  The correlation of neuropsychological outcome with the extent and location of ischemic
           lesions on brain CT-scan 12-21 days post-SAH, graded by the semi-quantitative
           ASPECT-grading

        -  Health-related quality of life at 3 months in patients with versus without DCI

        -  Home-time at 3 months in patients with versus without DCI

        -  Death and dependency at 3 months in patients with versus without DCI

        -  The absolute MoCA result, health-related quality of life and home-time at 3 months in
           patients with versus without hydrocephalus requiring shunting

        -  The absolute MoCA result, health-related quality of life and home-time at 3 months in
           patients with surgical versus endovascular aneurysm occlusion

      Key secondary endpoints for part 2 of the study are:

        -  The test/retest reliability of the MoCA in patients with acute brain damage

        -  The influence of the intensive care environment on the MoCA in patients with acute brain
           damage
observational model: Cohort
time perspective: Prospective
measure: Neuropsychological deterioration on the MoCA
time frame: 3 months after Subarachnoid Hemorrhage
description: The primary endpoint is the in-subject difference of the MoCA before (48-72h after aSAH) and after the active phase of DCI (3 months after aSAH) between patients with and without DCI. The MoCA scores will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI).
measure: Neuropsychological deterioration on the MoCA
time frame: Up to 28 days after Subarachnoid Hemorrhage (directly after the DCI phase)
description: As for the primary outcome, the MoCA at 14-28 days after aSAH will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI)
measure: Neuropsychological outcome
time frame: Up to 3 months after Subarachnoid Hemorrhage
description: Absolute results of the MoCA at 48-72h, 14-28 days and 3 months in patients that develop and those that do not develop DCI
measure: Reliability of the MoCA in patients with acute brain injury
time frame: Up to 1 month following acute brain injury
description: Reliability of the MoCA when tested in a (busy) intermediate care (IMC)/intensive care unit (ICU), as compared to the testing in a (quiet) setting in patients with acute brain injury.
measure: Test-retest reliability of the MoCA in patients with acute brain injury
time frame: Up to 1 month following acute brain injury
description: Test-retest reliability of the MoCA in patients with acute brain injury, tested two consecutive times with the MoCA (within 36 hours).
measure: Correlation between MoCA and CT-imaging
time frame: Up to 72 hours after Subarachnoid Hemorrhage
description: Correlation of the MoCA at 48-72h with the ASPECTS score for ischemic lesions on the CT-scan at 24-72h
measure: Correlation between MoCA and CT-imaging
time frame: Up to 28 days after Subarachnoid Hemorrhage (directly after the DCI phase)
description: Correlation of the MoCA at 14-28 days with the ASPECTS score for ischemic lesions on the CT-scan at 12-21 days
measure: Correlation between MoCA and CT-imaging
time frame: 3 months after Subarachnoid Hemorrhage
description: Correlation of the MoCA at 3 months with the ASPECTS score for ischemic lesions on the CT-scan between 6 weeks and 3 months
measure: Dependency/Mortality
time frame: 3 months after Subarachnoid Hemorrhage
description: Will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI) based on the mRS at 3 months, where modified Rankin Scale (mRS) 4 and 5 is considered as dependency, and mRS 6 is considered dead
measure: Health-related quality of life (HRQoL)
time frame: 3 months after Subarachnoid Hemorrhage
description: Will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI) using the Euro-Qol (EQ-5D)
measure: Shunt dependency (ventriculo-peritoneal or ventriculo-atrial shunt)
time frame: 3 months after Subarachnoid Hemorrhage
description: Will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI)
measure: Home time
time frame: 3 months after Subarachnoid Hemorrhage
description: Length of time (in days) spent in own home or relative's home since Subarachnoid Hemorrhage. Will be assessed by a neuropsychologist, not involved in the treatment of the patient and unaware of the patient's study group assignment (DCI vs. non-DCI)
measure: Minimum Clinically Important Difference (MCID) of the MoCA
time frame: Up to 3 months after Subarachnoid Hemorrhage
description: The MCID in patients with aneurysmal Subarachnoid Hemorrhage is determined using three different anchor-based approaches (using the GCS and NIHSS as anchors), namely the average change approach, minimum detectable change approach, and the change difference approach.
measure: Random number generation
time frame: Up to 1 month following acute brain injury
description: Random number generation, as a test of frontal executive functions in patients with acute brain injury will be assessed using the mental dice task by a neuropsychologist not involved in the treatment of the patient.
measure: Outcomes in patients with hydrocephalus vs. without hydrocephalus
time frame: Up to 3 months after Subarachnoid Hemorrhage
description: Outcomes 1, 2, 3 and 9-12 will be compared between patients that develop or do not develop hydrocephalus up to 3 months after Subarachnoid Hemorrhage.
measure: Outcomes in patiens treated surgically vs. endovascularly (aneurysm occlusion)
time frame: Up to 3 months after Subarachnoid Hemorrhage
description: Outcomes 1, 2, 3 and 9-12 will be compared between patients that are treated surgically or endovascularly up to 3 months after Subarachnoid Hemorrhage.
arm group label: DCI group
description: Patients that experience DCI, defined as
Cerebral infarction identified on imaging or proven at autopsy, after exclusion of procedure-related infarctions; and
Clinical deterioration caused by DCI, after exclusion of other potential causes of clinical deterioration will be assigned to the DCI group.
arm group label: non-DCI group
description: Patients not experiencing DCI as defined above.
intervention type: Other
intervention name: There is no intervention for this study. Patients are allocated to the study groups based on whether or not DCI occurs.
description: There is no intervention for this study. Patients are allocated to the study groups based on whether or not DCI occurs.
arm group label: DCI group
arm group label: non-DCI group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Subarachnoid Hemorrhage
mesh term: Cerebral Infarction
mesh term: Brain Ischemia
mesh term: Infarction
mesh term: Hemorrhage
mesh term: Ischemia
mesh term: Cognitive Dysfunction
mesh term: Cognition Disorders
study doc: 