<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/NCT01730690</url>
  </required_header>
  <id_info>
    <org_study_id>CRC11040</org_study_id>
    <secondary_id>NI11046</secondary_id>
    <nct_id>NCT01730690</nct_id>
  </id_info>
  <brief_title>Bacterial Meningitis in Adults: Analysis of the Determinants of Mortality and Neurosensory Sequelae</brief_title>
  <acronym>COMBAT</acronym>
  <official_title>Bacterial Meningitis in Adults: Analysis of the Determinants of Mortality and Neurosensory Sequelae</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Major changes in the epidemiological characteristics of bacterial meningitis have been&#xD;
      observed as a result of changes in behaviour, human interventions (use of antibiotics,&#xD;
      prophylactic vaccinations), as well as poorly elucidated mechanisms responsible for epidemic&#xD;
      outbreaks.&#xD;
&#xD;
      The objective of this study is to identify the determinants of in-hospital mortality of&#xD;
      bacterial meningitis in adults.&#xD;
&#xD;
      Hypothesis : the standardized data collection concerning cases of bacterial meningitis in&#xD;
      adults with telephone follow-up would allow analysis of the determinants of mortality and&#xD;
      neurosensory sequelae, description of the psychosocial impact and proposal of new treatment&#xD;
      strategies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction: Bacterial meningitis is a rare (about 1,200 cases per year in France, 50%&#xD;
      occurring in adults) and serious disease (20% mortality during the acute phase; neurosensory&#xD;
      sequelae in 30% of survivors). Major changes in the epidemiological characteristics of&#xD;
      bacterial meningitis have been observed as a result of changes in behaviour, human&#xD;
      interventions (use of antibiotics, prophylactic vaccinations), as well as poorly elucidated&#xD;
      mechanisms responsible for epidemic outbreaks. No standardized clinical, microbiological and&#xD;
      prognostic data collection concerning bacterial meningitis in adults is available in France.&#xD;
&#xD;
      Hypothesis: Standardized data collection concerning cases of bacterial meningitis in adults&#xD;
      with telephone follow-up would allow analysis of the determinants of mortality and&#xD;
      neurosensory sequelae, description of the psychosocial impact and proposal of new treatment&#xD;
      strategies.&#xD;
&#xD;
      Primary objective: To identify the determinants of in-hospital mortality of bacterial&#xD;
      meningitis in adults.&#xD;
&#xD;
      Secondary objectives: To describe the epidemiological characteristics of community-acquired&#xD;
      bacterial meningitis in adults, changes in these characteristics and their relations with the&#xD;
      vaccine status of the affected adult and his/her family; to characterize clinical and&#xD;
      microbiological failures and their determinants (pharmacological, microbiological,&#xD;
      immunological, etc.); to analyse the determinants of neurosensory sequelae and failure to&#xD;
      return to work after 1 month, 6 months and 12 months.&#xD;
&#xD;
      Primary endpoint: In-hospital mortality (D30). Secondary endpoints: History including&#xD;
      vaccination of the case and the family, clinical, microbiological (species, susceptibility,&#xD;
      virulence factors, cerebrospinal fluid CSF) culture on D0 and H48), imaging characteristics;&#xD;
      treatments, CSF antibiotic concentrations, neurological sequelae (modified Rankin, Glasgow&#xD;
      Outcome Scale, IQCODE) at M1, M6 an M12, quality of life test SF12, WHO QoL, CESD) at M1, M6,&#xD;
      M12, hearing loss (audiometric tests, hereditary hearing impairment (HHI), telephone speech&#xD;
      test in noise) at M1, M6, M12.&#xD;
&#xD;
      Methodology, study design: National observational cohort study with comprehensive recruitment&#xD;
      in participating centres.&#xD;
&#xD;
      Legal classification of the project: Epidemiological study. Number of subjects required: The&#xD;
      inclusion of 150 cases of meningitis per year would allow the collection of about 450 cases&#xD;
      over a period of 3 years. For a mortality rate of 20%, we would be able to estimate this&#xD;
      percentage with a confidence interval of ± 3.7% (95% confidence interval: 16.3-23.7). With 90&#xD;
      deaths, a power of 80% and a level of significance of 5% (two-tailed), this sample size would&#xD;
      demonstrate relative risks of 1.8 for a prevalence of the risk factor of 25% and 2.6 for a&#xD;
      prevalence of the risk factor of 10%.&#xD;
&#xD;
      Inclusion criteria: Adult with community-acquired bacterial meningitis defined by the&#xD;
      presence of at least one of the following criteria: 1/ Positive CSF culture and/or positive&#xD;
      soluble antigen in CSF with or without cell reaction; 2/ Positive PCR in CSF; 3/ Purpura&#xD;
      fulminant (with or without positive CSF culture); Positive polymerase chain reaction (PCR) in&#xD;
      blood and/or positive blood culture AND CSF cell reaction.&#xD;
&#xD;
      Non inclusion criteria: Age less than 18 years old or refusal to participate. Inclusion&#xD;
      period: 3 years. Duration of participation for one patient: 12 months. Number of&#xD;
      participating centers: Constitution in participating centers of a dual investigator team&#xD;
      comprising a clinician (infectious diseases physician, intensive care physician, or&#xD;
      neurologist) and a microbiologist (participating in the national network of &quot;OBSERVATOIRES&#xD;
      REGIONAUX DU PNEUMOCOQUE&quot; [Regional Pneumococcal Observatories]). Declaration by the&#xD;
      microbiologist to the data management centre. On-site validation of cases by the dual&#xD;
      investigator team and then by a national multidisciplinary validation unit.&#xD;
&#xD;
      Mean number of inclusions per month and per centre: 0.5&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</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>In-hospital mortality</measure>
    <time_frame>30 days</time_frame>
    <description>mortality in hospital at 30 days</description>
  </primary_outcome>
  <enrollment type="Actual">527</enrollment>
  <condition>Meningitis, Bacterial</condition>
  <eligibility>
    <study_pop>
      <textblock>
        patients with bacterial meningitis adults&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Positive CSF culture and/or positive soluble antigens in CSF with or without a cell&#xD;
             reaction&#xD;
&#xD;
          -  Positive PCR in CSF&#xD;
&#xD;
          -  Purpura fulminant (with or without positive CSF culture)&#xD;
&#xD;
          -  Positive PCR in blood and/or positive blood culture AND CSF cell reaction.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 18 years old&#xD;
&#xD;
          -  Refusal to participate&#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>Xavier duval</last_name>
    <role>Principal Investigator</role>
    <affiliation>APHP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Assistance Publique des Hôpitaux de Paris</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>July 3, 2017</last_update_submitted>
  <last_update_submitted_qc>July 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bacterial meningitis in adults</keyword>
  <keyword>determinants of in-hospital mortality</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meningitis, Bacterial</mesh_term>
    <mesh_term>Meningitis</mesh_term>
  </condition_browse>
  <!-- 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/NCT01730690
org study id: CRC11040
secondary id: NI11046
nct id: NCT01730690
lead sponsor: 
has dmc: No
Major changes in the epidemiological characteristics of bacterial meningitis have been
      observed as a result of changes in behaviour, human interventions (use of antibiotics,
      prophylactic vaccinations), as well as poorly elucidated mechanisms responsible for epidemic
      outbreaks.

      The objective of this study is to identify the determinants of in-hospital mortality of
      bacterial meningitis in adults.

      Hypothesis : the standardized data collection concerning cases of bacterial meningitis in
      adults with telephone follow-up would allow analysis of the determinants of mortality and
      neurosensory sequelae, description of the psychosocial impact and proposal of new treatment
      strategies.
Introduction: Bacterial meningitis is a rare (about 1,200 cases per year in France, 50%
      occurring in adults) and serious disease (20% mortality during the acute phase; neurosensory
      sequelae in 30% of survivors). Major changes in the epidemiological characteristics of
      bacterial meningitis have been observed as a result of changes in behaviour, human
      interventions (use of antibiotics, prophylactic vaccinations), as well as poorly elucidated
      mechanisms responsible for epidemic outbreaks. No standardized clinical, microbiological and
      prognostic data collection concerning bacterial meningitis in adults is available in France.

      Hypothesis: Standardized data collection concerning cases of bacterial meningitis in adults
      with telephone follow-up would allow analysis of the determinants of mortality and
      neurosensory sequelae, description of the psychosocial impact and proposal of new treatment
      strategies.

      Primary objective: To identify the determinants of in-hospital mortality of bacterial
      meningitis in adults.

      Secondary objectives: To describe the epidemiological characteristics of community-acquired
      bacterial meningitis in adults, changes in these characteristics and their relations with the
      vaccine status of the affected adult and his/her family; to characterize clinical and
      microbiological failures and their determinants (pharmacological, microbiological,
      immunological, etc.); to analyse the determinants of neurosensory sequelae and failure to
      return to work after 1 month, 6 months and 12 months.

      Primary endpoint: In-hospital mortality (D30). Secondary endpoints: History including
      vaccination of the case and the family, clinical, microbiological (species, susceptibility,
      virulence factors, cerebrospinal fluid CSF) culture on D0 and H48), imaging characteristics;
      treatments, CSF antibiotic concentrations, neurological sequelae (modified Rankin, Glasgow
      Outcome Scale, IQCODE) at M1, M6 an M12, quality of life test SF12, WHO QoL, CESD) at M1, M6,
      M12, hearing loss (audiometric tests, hereditary hearing impairment (HHI), telephone speech
      test in noise) at M1, M6, M12.

      Methodology, study design: National observational cohort study with comprehensive recruitment
      in participating centres.

      Legal classification of the project: Epidemiological study. Number of subjects required: The
      inclusion of 150 cases of meningitis per year would allow the collection of about 450 cases
      over a period of 3 years. For a mortality rate of 20%, we would be able to estimate this
      percentage with a confidence interval of ± 3.7% (95% confidence interval: 16.3-23.7). With 90
      deaths, a power of 80% and a level of significance of 5% (two-tailed), this sample size would
      demonstrate relative risks of 1.8 for a prevalence of the risk factor of 25% and 2.6 for a
      prevalence of the risk factor of 10%.

      Inclusion criteria: Adult with community-acquired bacterial meningitis defined by the
      presence of at least one of the following criteria: 1/ Positive CSF culture and/or positive
      soluble antigen in CSF with or without cell reaction; 2/ Positive PCR in CSF; 3/ Purpura
      fulminant (with or without positive CSF culture); Positive polymerase chain reaction (PCR) in
      blood and/or positive blood culture AND CSF cell reaction.

      Non inclusion criteria: Age less than 18 years old or refusal to participate. Inclusion
      period: 3 years. Duration of participation for one patient: 12 months. Number of
      participating centers: Constitution in participating centers of a dual investigator team
      comprising a clinician (infectious diseases physician, intensive care physician, or
      neurologist) and a microbiologist (participating in the national network of "OBSERVATOIRES
      REGIONAUX DU PNEUMOCOQUE" [Regional Pneumococcal Observatories]). Declaration by the
      microbiologist to the data management centre. On-site validation of cases by the dual
      investigator team and then by a national multidisciplinary validation unit.

      Mean number of inclusions per month and per centre: 0.5
observational model: Cohort
time perspective: Prospective
measure: In-hospital mortality
time frame: 30 days
description: mortality in hospital at 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: Xavier duval
role: Principal Investigator
affiliation: APHP
facility: 
country: France
responsible party type: Sponsor
mesh term: Meningitis, Bacterial
mesh term: Meningitis