<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/NCT04467762</url>
  </required_header>
  <id_info>
    <org_study_id>A 2020-0160</org_study_id>
    <nct_id>NCT04467762</nct_id>
  </id_info>
  <brief_title>Neurocognitive Impairment in Pediatric Patients With Meningoencephalitis and Sepsis-associated Encephalopathy</brief_title>
  <acronym>NCIPED</acronym>
  <official_title>Incidence and Severity of Neurocognitive Impairment in Pediatric Patients With Meningoencephalitis and Sepsis-associated Encephalopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rostock</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Rostock</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>
      Neurocognitive impairment is frequently observed in pediatric patients with&#xD;
      meningoencephalitis (ME) and sepsis-associated encephalopathy (SAE) which represent two&#xD;
      relevant central nervous system (CNS) diseases in pediatric patients. It is uncertain, if the&#xD;
      the origin of the disease, located primarily in the CNS of patients with ME or secondarily in&#xD;
      patients with SAE in the course of sepsis, is of importance for the severity of injury to the&#xD;
      brain. Prospective clinical studies combining clinical and laboratory examinations including&#xD;
      specific biomarkers of neuroaxonal injury were not performed in a comparative study.&#xD;
      Biomarkers of neuroaxonal injury are therefore not only of great interest to detect and&#xD;
      monitor neurocognitive impairment but also to quantify the severity of brain injury in&#xD;
      patients with ME and SAE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective single-center observational study evaluating the incidence and severity&#xD;
      of the neurocognitive impairment in pediatric patients with meningoencephalitis (ME) and&#xD;
      sepsis-associated encephalopathy (SAE). All study participants will be assessed by clinical&#xD;
      and neurological examination as well as comprehensive laboratory tests using biomarkers of&#xD;
      neuroaxonal injury at study day 1 (day of study inclusion), day 3 and day 5. A panel of&#xD;
      biomarkers derived from blood and cerebrospinal fluid (CSF) samples (among others NSE, S100B&#xD;
      and neurofilament proteins) will be measured. Clinical assessment will be performed using&#xD;
      validated scales of severity of disease (e.g. pSOFA score) and validated delirium tests&#xD;
      (among others pGCS, pCAM-ICU) to assess the neurocognitive performance of study participants&#xD;
      before and three months after study inclusion (among others POPC/PCPC).&#xD;
&#xD;
      A matched group of pediatric patients without evidence for ME or sepsis/SAE will serve as a&#xD;
      control group and will undergo the same clinical and laboratory examinations except CSF&#xD;
      analysis.&#xD;
&#xD;
      The investigators hypothesize, that:&#xD;
&#xD;
        1. Patients with ME (primary CNS infection) indicate a higher incidence and severity of&#xD;
           neurocognitive impairment than patients with SAE (secondary CNS affection)&#xD;
&#xD;
        2. Specific biomarkers of neuroaxonal injury in blood and CSF correlate with the clinical&#xD;
           severity of neurocognitive impairment in patients with ME and SAE&#xD;
&#xD;
        3. Specific biomarkers of neuroaxonal injury in blood and CSF correlate with the 3-months&#xD;
           neurocognitive outcome of patients with ME and SAE&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 3, 2020</start_date>
  <completion_date type="Actual">October 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of delirium/neurocognitive impairment in pediatric patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy</measure>
    <time_frame>Day 90</time_frame>
    <description>Assessment of neurocognitive impairment using validated tools</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in neuroaxonal injury biomarker levels in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy</measure>
    <time_frame>Change from baseline biomarker levels at day 5</time_frame>
    <description>Measurement of biomarker levels (e.g. NSE, S100B, neurofilament proteins) derived from blood and cerebrospinal fluid samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurocognitive 3-months outcome in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy</measure>
    <time_frame>Day 90</time_frame>
    <description>Assessment of the neurocognitive performance of patients using validated tests (e.g. pediatric cerebral performance category)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>90-day survival in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy</measure>
    <time_frame>Day 90</time_frame>
    <description>Survival after 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy</measure>
    <time_frame>1 year</time_frame>
    <description>Cumulative days in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of intensive care unit stay in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy</measure>
    <time_frame>1 year</time_frame>
    <description>Cumulative days on intensive care unit</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">42</enrollment>
  <condition>Critical Illness</condition>
  <condition>Brain Injuries</condition>
  <condition>Encephalopathy</condition>
  <condition>Delirium</condition>
  <condition>Inflammatory Disease</condition>
  <condition>Central Nervous System Diseases</condition>
  <arm_group>
    <arm_group_label>Meningoencephalitis (ME-PED)</arm_group_label>
    <description>pediatric patients between 0 and 17 years of age&#xD;
admission to hospital with suspected meningoencephalitis&#xD;
confirmed meningoencephalitis within 24 hours after admission</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sepsis-associated encephalopathy (SAE-PED)</arm_group_label>
    <description>pediatric patients between 0 and 17 years of age&#xD;
admission to hospital with suspected sepsis&#xD;
confirmed sepsis within 24 hours after admission or time of diagnosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group (CON-PED)</arm_group_label>
    <description>pediatric patients between 0 and 17 years of age&#xD;
exclusion of neurocognitive impairment&#xD;
admission to hospital for minor surgery (e.g. herniotomy, adenoidectomy, fractures treated by osteosynthesis) or for hemangioma treated by propranolol</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and cerebrospinal fluid samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All pediatric patients who are admitted to the study center will be screened for study&#xD;
        eligibility according to the inclusion and exclusion criteria.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pediatric patients between 1 day and 17 years of age&#xD;
&#xD;
          -  admission to hospital with suspected meningoencephalitis or sepsis &lt;24 hours after&#xD;
             admission or time of diagnosis&#xD;
&#xD;
          -  admission to hospital for minor surgery (herniotomy, osteosynthesis, adenoidectomy)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  preexisting central nervous system diseases (stroke, hemorrhage, tumor, traumatic&#xD;
             brain injury, brain surgery, epilepsy, hydrocephalus)&#xD;
&#xD;
          -  preexisting immunosuppression&#xD;
&#xD;
          -  participation in another interventional study&#xD;
&#xD;
          -  no written informed consent from parents or legal representative&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Johannes Ehler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rostock</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Center Rostock</name>
      <address>
        <city>Rostock</city>
        <zip>18059</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rostock</investigator_affiliation>
    <investigator_full_name>Dr. Johannes Ehler, MD</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meningoencephalitis</mesh_term>
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
    <mesh_term>Central Nervous System Diseases</mesh_term>
    <mesh_term>Sepsis-Associated Encephalopathy</mesh_term>
    <mesh_term>Critical Illness</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/NCT04467762
org study id: A 2020-0160
nct id: NCT04467762
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Neurocognitive impairment is frequently observed in pediatric patients with
      meningoencephalitis (ME) and sepsis-associated encephalopathy (SAE) which represent two
      relevant central nervous system (CNS) diseases in pediatric patients. It is uncertain, if the
      the origin of the disease, located primarily in the CNS of patients with ME or secondarily in
      patients with SAE in the course of sepsis, is of importance for the severity of injury to the
      brain. Prospective clinical studies combining clinical and laboratory examinations including
      specific biomarkers of neuroaxonal injury were not performed in a comparative study.
      Biomarkers of neuroaxonal injury are therefore not only of great interest to detect and
      monitor neurocognitive impairment but also to quantify the severity of brain injury in
      patients with ME and SAE.
This is a prospective single-center observational study evaluating the incidence and severity
      of the neurocognitive impairment in pediatric patients with meningoencephalitis (ME) and
      sepsis-associated encephalopathy (SAE). All study participants will be assessed by clinical
      and neurological examination as well as comprehensive laboratory tests using biomarkers of
      neuroaxonal injury at study day 1 (day of study inclusion), day 3 and day 5. A panel of
      biomarkers derived from blood and cerebrospinal fluid (CSF) samples (among others NSE, S100B
      and neurofilament proteins) will be measured. Clinical assessment will be performed using
      validated scales of severity of disease (e.g. pSOFA score) and validated delirium tests
      (among others pGCS, pCAM-ICU) to assess the neurocognitive performance of study participants
      before and three months after study inclusion (among others POPC/PCPC).

      A matched group of pediatric patients without evidence for ME or sepsis/SAE will serve as a
      control group and will undergo the same clinical and laboratory examinations except CSF
      analysis.

      The investigators hypothesize, that:

        1. Patients with ME (primary CNS infection) indicate a higher incidence and severity of
           neurocognitive impairment than patients with SAE (secondary CNS affection)

        2. Specific biomarkers of neuroaxonal injury in blood and CSF correlate with the clinical
           severity of neurocognitive impairment in patients with ME and SAE

        3. Specific biomarkers of neuroaxonal injury in blood and CSF correlate with the 3-months
           neurocognitive outcome of patients with ME and SAE
observational model: Case-Control
time perspective: Prospective
measure: Incidence of delirium/neurocognitive impairment in pediatric patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy
time frame: Day 90
description: Assessment of neurocognitive impairment using validated tools
measure: Change in neuroaxonal injury biomarker levels in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy
time frame: Change from baseline biomarker levels at day 5
description: Measurement of biomarker levels (e.g. NSE, S100B, neurofilament proteins) derived from blood and cerebrospinal fluid samples
measure: Neurocognitive 3-months outcome in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy
time frame: Day 90
description: Assessment of the neurocognitive performance of patients using validated tests (e.g. pediatric cerebral performance category)
measure: 90-day survival in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy
time frame: Day 90
description: Survival after 90 days
measure: Length of hospital stay in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy
time frame: 1 year
description: Cumulative days in hospital
measure: Length of intensive care unit stay in patients with meningoencephalitis compared to patients with sepsis-associated encephalopathy
time frame: 1 year
description: Cumulative days on intensive care unit
arm group label: Meningoencephalitis (ME-PED)
description: pediatric patients between 0 and 17 years of age
admission to hospital with suspected meningoencephalitis
confirmed meningoencephalitis within 24 hours after admission
arm group label: Sepsis-associated encephalopathy (SAE-PED)
description: pediatric patients between 0 and 17 years of age
admission to hospital with suspected sepsis
confirmed sepsis within 24 hours after admission or time of diagnosis
arm group label: Control group (CON-PED)
description: pediatric patients between 0 and 17 years of age
exclusion of neurocognitive impairment
admission to hospital for minor surgery (e.g. herniotomy, adenoidectomy, fractures treated by osteosynthesis) or for hemangioma treated by propranolol
Blood and cerebrospinal fluid samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Day
maximum age: 17 Years
healthy volunteers: No
last name: Johannes Ehler, MD
role: Principal Investigator
affiliation: University of Rostock
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University of Rostock
investigator full name: Dr. Johannes Ehler, MD
investigator title: Principal investigator
mesh term: Meningoencephalitis
mesh term: Brain Injuries
mesh term: Brain Diseases
mesh term: Nervous System Diseases
mesh term: Central Nervous System Diseases
mesh term: Sepsis-Associated Encephalopathy
mesh term: Critical Illness
sharing ipd: No