<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/NCT03010709</url>
  </required_header>
  <id_info>
    <org_study_id>A094232</org_study_id>
    <nct_id>NCT03010709</nct_id>
  </id_info>
  <brief_title>Multimodality Monitoring Directed Management of Aneurysmal Subarachnoid Haemorrhage</brief_title>
  <acronym>MMMSAH</acronym>
  <official_title>Multimodality Monitoring Directed Management of Aneurysmal Subarachnoid Haemorrhage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adel Helmy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Cambridge</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aneurysmal subarachnoid haemorrhage (aSAH) affects up to 10,000 individuals per year in the&#xD;
      UK. It accounts for ~5% of strokes, but is responsible for about 25% quality-adjusted life&#xD;
      years (QALYs) lost due to stroke. Although early repair of ruptured aneurysms and aggressive&#xD;
      postoperative management has improved overall outcomes, it remains a devastating disease with&#xD;
      mortality approaching 50%. Survivors are left with neurological injuries that range from&#xD;
      subtle cognitive deficit to disabling cerebral infarctions, less than 60% them returning to&#xD;
      functional independence.&#xD;
&#xD;
      SAH triggers a series of pathological processes resulting in neuronal damage and consequent&#xD;
      neurological deficit termed early brain injury (EBI). Many of the patients who survive the&#xD;
      initial bleed, deteriorate days later from delayed ischaemic neurological deficit (DIND),&#xD;
      which causes poor outcome or death in up to 30% of patients with SAH. Both of these&#xD;
      pathological processes are still poorly understood which limits the number of treatment&#xD;
      options.&#xD;
&#xD;
      DIND is treated with blood pressure augmentation to ensure adequate blood flow in the brain.&#xD;
      In awake patients, response can be easily and accurately assessed by performing a thorough&#xD;
      neurological examination. In patients whose clinical condition demands sedation, intubation&#xD;
      and ventilation, assessing response to treatment using the neurological examination is&#xD;
      virtually impossible. Multimodality monitoring (MM), primarily microdialysis and brain tissue&#xD;
      oxygen tension with catheters inserted into the relevant parts of the brain offer direct&#xD;
      assessment of both delivery and utilisation of metabolic substrates at the cellular level.&#xD;
      These can be used for early detection of DIND as well as monitoring during blood pressure&#xD;
      augmentation. The aim of this study is to establish and validate a clinical protocol for MM&#xD;
      derived management of SAH patients, to determine optimal therapies for correcting&#xD;
      abnormalities in brain metabolism and explore the relationship between MD and other&#xD;
      monitoring modalities.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective observational study of patients with poor grade subarachnoid&#xD;
      haemorrhage (SAH) caused by a ruptured brain artery aneurysm. The investigators aim to&#xD;
      include 100 patients over a 5-year period.&#xD;
&#xD;
      SAH is diagnosed using computer tomography imaging of the brain and the presence of a&#xD;
      ruptured aneurysm by means of computer tomography angiogram of the vessels of the head. These&#xD;
      two investigations are part of the standard clinical practice for every patient with&#xD;
      suspected SAH. Term ''poor grade'' is used for cases of SAH where the patient is unconscious&#xD;
      i.e. in a coma as a consequence of this disease and whose clinical condition requires&#xD;
      intubation and ventilation (with or without sedation) and thus admission to an intensive care&#xD;
      unit. All patients with poor grade SAH admitted to the neurosciences critical care unit will&#xD;
      be screened for participation in this study. All poor grade SAH patients are unconscious and&#xD;
      thus unable to give informed consent. Therefore, the next-of-kin of all eligible patients&#xD;
      will be approached to discuss and consider patient's involvement in the study. If there is no&#xD;
      next-of-kin, the treating clinician will be approached as a professional consultee.&#xD;
&#xD;
      Once consent is obtained from next-of-kin, the participants will have the following&#xD;
      monitoring instituted:&#xD;
&#xD;
        1. An intracranial access device will be inserted under general anaesthesia with an&#xD;
           intracranial pressure (ICP), a Licox partial tension of tissue oxygen (PbtO2) probe and&#xD;
           a microdialysis (MD) catheter. Neuromonitors will be inserted into the part of the brain&#xD;
           that is supplied by the affected artery. This procedure will be performed on the&#xD;
           neurocritical care unit or in theatre if patients are undergoing other operative&#xD;
           procedures at the same time. Continuous neuromonitoring will commence. Hourly MD samples&#xD;
           will be processed and the leftover samples stored in -80oC for cytokine analysis at a&#xD;
           later date. Neuromonitoring will continue for as long as clinically needed and up to 21&#xD;
           days from ictus.&#xD;
&#xD;
        2. All participants will be fitted with a near-infrared spectroscopy monitor (NIRS) . This&#xD;
           non-invasive monitor is used to measure tissue haemoglobin concentration and oxygen&#xD;
           content continuously and at the bedside.&#xD;
&#xD;
        3. Daily transcranial Doppler (TCD) examinations will be performed at the bedside to assess&#xD;
           the caliber of large cerebral arteries. This procedure is used in regular clinical&#xD;
           practice to diagnose large vessel spasm which is one of the pathological substrates for&#xD;
           delayed cerebral ischaemia (DCI) All participants will have a CT brain perfusion scan&#xD;
           between day 3 and day 5 from the initial haemorrhage (ictus) or when clinically needed&#xD;
           to assess brain perfusion and possibility of DCI which is part of standard clinical&#xD;
           practice. These scans are reviewed and reported by consultant neuroradiologists. If they&#xD;
           identify an area (or areas) of reversible ischaemia, researchers will review the&#xD;
           position of invasive brain monitors - if these are outside of the area of DCI,&#xD;
           additional monitors will be inserted into the identified area of reversible ishaemia.&#xD;
           Researchers will then use invasive brain monitors (MD and LiCox) and non-invasive&#xD;
           monitoring (NIRS and TCD) to assess the response to standard treatment of cerebral&#xD;
           reversible ischaemia which is hypertensive therapy i.e. mean arterial pressure (MAP)&#xD;
           augmentation with vasoactive medications.&#xD;
&#xD;
      Repeat CT brain perfusion scan will be performed between days 7 and 10 from the initial&#xD;
      haemorrhage or earlier if clinically indicated to assess response to treatment.&#xD;
&#xD;
      Following a 6 month period, researchers will see the patients in outpatient clinic to assess&#xD;
      functional outcome. This is part of the patient's standard clinical care as all our patients&#xD;
      are offered clinical follow up in this way.&#xD;
&#xD;
      Researchers will collect any biological samples that are available as part of the standard&#xD;
      clinical care of the participant and will not subject the participants to any additional&#xD;
      procedures. This would consist of:&#xD;
&#xD;
        -  left over microdialysate samples that are not used for the standard clinical care of the&#xD;
           participant&#xD;
&#xD;
        -  daily blood samples if the participant has an arterial line or central venous catheter&#xD;
&#xD;
        -  samples of cerebrospinal fluid (CSF) if the participant has an external ventricular&#xD;
           drain&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>February 2017</start_date>
  <completion_date type="Anticipated">February 2022</completion_date>
  <primary_completion_date type="Anticipated">February 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>Improvement in brain tissue oxygen tension</measure>
    <time_frame>10 days</time_frame>
    <description>Brain Tissue Oxygen measured continuously on Neurointensive Care.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lactate to pyruvate ratio measured by microdialysis</measure>
    <time_frame>10 days</time_frame>
    <description>Microdialysis measured LP ratio measured hourly on Neurointensive Care.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improved functional outcome of patients as measured by the validated and widely used Extended Glasgow Outcome Scale</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Subarachnoid Hemorrhage, Aneurysmal</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Microdialysates, cerebrospinal fluid and blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patient with aneurysmal subarachnoid haemorrhage who require intubation and ventilation and&#xD;
        admission to the critical care unit.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aneurysmal Subarachnoid Haemorrhage&#xD;
&#xD;
          -  Patient in Neurosciences Critical Care Unit&#xD;
&#xD;
          -  Patient likely to survive for at least 24 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient unsuitable for microdialysis monitoring&#xD;
&#xD;
               -  bleeding diathesis&#xD;
&#xD;
               -  thrombocytopaenia (platelets &lt; 100 x 10e9 per litre)&#xD;
&#xD;
          2. Non-survivable brain injury i.e. patient not expected to survive more than 24 hours&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adel Helmy, MBBChir PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cambridge University Hospitals NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Adel Helmy, MBBChir PhD</last_name>
    <phone>07855064515</phone>
    <email>adelhelmy@doctors.org.uk</email>
  </overall_contact>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>January 3, 2017</last_update_submitted>
  <last_update_submitted_qc>January 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Cambridge</investigator_affiliation>
    <investigator_full_name>Adel Helmy</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Aneurysmal Subarachnoid Haemorrhage</keyword>
  <keyword>Delayed Ischaemic Neurological Deficit</keyword>
  <keyword>Induced Hypertension</keyword>
  <keyword>Partial Brain Tissue Oxygen Tension</keyword>
  <keyword>Cerebral Microdialysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Subarachnoid Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</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/NCT03010709
org study id: A094232
nct id: NCT03010709
lead sponsor: 
collaborator: 
has dmc: No
Aneurysmal subarachnoid haemorrhage (aSAH) affects up to 10,000 individuals per year in the
      UK. It accounts for ~5% of strokes, but is responsible for about 25% quality-adjusted life
      years (QALYs) lost due to stroke. Although early repair of ruptured aneurysms and aggressive
      postoperative management has improved overall outcomes, it remains a devastating disease with
      mortality approaching 50%. Survivors are left with neurological injuries that range from
      subtle cognitive deficit to disabling cerebral infarctions, less than 60% them returning to
      functional independence.

      SAH triggers a series of pathological processes resulting in neuronal damage and consequent
      neurological deficit termed early brain injury (EBI). Many of the patients who survive the
      initial bleed, deteriorate days later from delayed ischaemic neurological deficit (DIND),
      which causes poor outcome or death in up to 30% of patients with SAH. Both of these
      pathological processes are still poorly understood which limits the number of treatment
      options.

      DIND is treated with blood pressure augmentation to ensure adequate blood flow in the brain.
      In awake patients, response can be easily and accurately assessed by performing a thorough
      neurological examination. In patients whose clinical condition demands sedation, intubation
      and ventilation, assessing response to treatment using the neurological examination is
      virtually impossible. Multimodality monitoring (MM), primarily microdialysis and brain tissue
      oxygen tension with catheters inserted into the relevant parts of the brain offer direct
      assessment of both delivery and utilisation of metabolic substrates at the cellular level.
      These can be used for early detection of DIND as well as monitoring during blood pressure
      augmentation. The aim of this study is to establish and validate a clinical protocol for MM
      derived management of SAH patients, to determine optimal therapies for correcting
      abnormalities in brain metabolism and explore the relationship between MD and other
      monitoring modalities.
This is a prospective observational study of patients with poor grade subarachnoid
      haemorrhage (SAH) caused by a ruptured brain artery aneurysm. The investigators aim to
      include 100 patients over a 5-year period.

      SAH is diagnosed using computer tomography imaging of the brain and the presence of a
      ruptured aneurysm by means of computer tomography angiogram of the vessels of the head. These
      two investigations are part of the standard clinical practice for every patient with
      suspected SAH. Term ''poor grade'' is used for cases of SAH where the patient is unconscious
      i.e. in a coma as a consequence of this disease and whose clinical condition requires
      intubation and ventilation (with or without sedation) and thus admission to an intensive care
      unit. All patients with poor grade SAH admitted to the neurosciences critical care unit will
      be screened for participation in this study. All poor grade SAH patients are unconscious and
      thus unable to give informed consent. Therefore, the next-of-kin of all eligible patients
      will be approached to discuss and consider patient's involvement in the study. If there is no
      next-of-kin, the treating clinician will be approached as a professional consultee.

      Once consent is obtained from next-of-kin, the participants will have the following
      monitoring instituted:

        1. An intracranial access device will be inserted under general anaesthesia with an
           intracranial pressure (ICP), a Licox partial tension of tissue oxygen (PbtO2) probe and
           a microdialysis (MD) catheter. Neuromonitors will be inserted into the part of the brain
           that is supplied by the affected artery. This procedure will be performed on the
           neurocritical care unit or in theatre if patients are undergoing other operative
           procedures at the same time. Continuous neuromonitoring will commence. Hourly MD samples
           will be processed and the leftover samples stored in -80oC for cytokine analysis at a
           later date. Neuromonitoring will continue for as long as clinically needed and up to 21
           days from ictus.

        2. All participants will be fitted with a near-infrared spectroscopy monitor (NIRS) . This
           non-invasive monitor is used to measure tissue haemoglobin concentration and oxygen
           content continuously and at the bedside.

        3. Daily transcranial Doppler (TCD) examinations will be performed at the bedside to assess
           the caliber of large cerebral arteries. This procedure is used in regular clinical
           practice to diagnose large vessel spasm which is one of the pathological substrates for
           delayed cerebral ischaemia (DCI) All participants will have a CT brain perfusion scan
           between day 3 and day 5 from the initial haemorrhage (ictus) or when clinically needed
           to assess brain perfusion and possibility of DCI which is part of standard clinical
           practice. These scans are reviewed and reported by consultant neuroradiologists. If they
           identify an area (or areas) of reversible ischaemia, researchers will review the
           position of invasive brain monitors - if these are outside of the area of DCI,
           additional monitors will be inserted into the identified area of reversible ishaemia.
           Researchers will then use invasive brain monitors (MD and LiCox) and non-invasive
           monitoring (NIRS and TCD) to assess the response to standard treatment of cerebral
           reversible ischaemia which is hypertensive therapy i.e. mean arterial pressure (MAP)
           augmentation with vasoactive medications.

      Repeat CT brain perfusion scan will be performed between days 7 and 10 from the initial
      haemorrhage or earlier if clinically indicated to assess response to treatment.

      Following a 6 month period, researchers will see the patients in outpatient clinic to assess
      functional outcome. This is part of the patient's standard clinical care as all our patients
      are offered clinical follow up in this way.

      Researchers will collect any biological samples that are available as part of the standard
      clinical care of the participant and will not subject the participants to any additional
      procedures. This would consist of:

        -  left over microdialysate samples that are not used for the standard clinical care of the
           participant

        -  daily blood samples if the participant has an arterial line or central venous catheter

        -  samples of cerebrospinal fluid (CSF) if the participant has an external ventricular
           drain
observational model: Cohort
time perspective: Prospective
measure: Improvement in brain tissue oxygen tension
time frame: 10 days
description: Brain Tissue Oxygen measured continuously on Neurointensive Care.
measure: Lactate to pyruvate ratio measured by microdialysis
time frame: 10 days
description: Microdialysis measured LP ratio measured hourly on Neurointensive Care.
measure: Improved functional outcome of patients as measured by the validated and widely used Extended Glasgow Outcome Scale
time frame: 6 months
Microdialysates, cerebrospinal fluid and blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Adel Helmy, MBBChir PhD
role: Principal Investigator
affiliation: Cambridge University Hospitals NHS Foundation Trust
last name: Adel Helmy, MBBChir PhD
phone: 07855064515
email: adelhelmy@doctors.org.uk
responsible party type: Sponsor-Investigator
investigator affiliation: University of Cambridge
investigator full name: Adel Helmy
investigator title: Principal Investigator
mesh term: Subarachnoid Hemorrhage
mesh term: Hemorrhage
sharing ipd: No