Meningitis, BacterialCOMBATNCT01730690
Bacterial Meningitis in Adults: Analysis of the Determinants of Mortality and Neurosensory Sequelae
An observational study of Meningitis, Bacterial, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Meningitis, Bacterial
- How many people
- 527 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2013to Jun 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients with bacterial meningitis adults
Who may be able to join
- Positive CSF culture and/or positive soluble antigens in CSF with or without a cell reaction
- Positive PCR in CSF
- Purpura fulminant (with or without positive CSF culture)
- Positive PCR in blood and/or positive blood culture AND CSF cell reaction.
Who cannot join
- Age less than 18 years old
- Refusal to participate
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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
- Conditions
- Meningitis, Bacterial
- Keywords
- Bacterial meningitis in adults, determinants of in-hospital mortality
- Medical subject headings
- Meningitis, Bacterial
What is being measured
The primary outcome is the main question the study is designed to answer.
In-hospital mortality
mortality in hospital at 30 days
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2012 (estimated)
- Study startMar 2013
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Meningitis, BacterialStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 527 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xavier duval, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01730690
- Sponsor's protocol ID
- CRC11040
- Other IDs
- NI11046
- Acronym
- COMBAT
- Status last verified
- Jul 2017
- First submitted
- 15 Nov 2012
- Last updated
- 5 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
de Villiers de la Noue V, Tubiana S, Rontani M, Giry M, Sarton B, Pommier JD, Terzi N, Jozwiak M, Argaud L, Dupuis C, Marin N, Quenot JP, Nedelec P, Garcia M, Barbier F, Kuteifan K, Benchabane N, Duval X, Mourvillier B; COMBAT cohort study. Prognostic factors in ICU patients with community-acquired bacterial meningitis: A post hoc analysis of a multicenter prospective cohort study. J Intensive Med. 2026 Jun 13;6(5):524-533. doi: 10.1016/j.jointm.2026.04.007. eCollection 2026 Oct.
PubMed 42979101Van RN, Tubiana S, De Broucker T, Cedric J, Roy C, Meyohas MC, Prazuck T, Chirouze C, Hoen B, Duval X, Revest M; COMBAT study group. Persistent headaches one year after bacterial meningitis: prevalence, determinants and impact on quality of life. Eur J Clin Microbiol Infect Dis. 2023 Dec;42(12):1459-1467. doi: 10.1007/s10096-023-04673-y. Epub 2023 Oct 23.
PubMed 37867184Della Vecchia C, Ebah JV, Tubiana S, Guimard T, Piroth L, Jaffuel S, Gorenne I, Mourvillier B, Hoen B, Duval X, Preau M. Mid-term health-related quality of life in community-acquired bacterial meningitis survivors; the COMBAT study. PLoS One. 2023 Mar 23;18(3):e0281544. doi: 10.1371/journal.pone.0281544. eCollection 2023.
PubMed 36952472Akroum S, Tubiana S, de Broucker T, Dournon N, Varon E, Ploy MC, Mourvillier B, Oziol E, Lacassin F, Laurichesse H, Hoen B, Duval X, Burdet C; and the COMBAT study group. Long-term neuro-functional disability in adult patients with community-acquired bacterial meningitis. Infection. 2022 Oct;50(5):1363-1372. doi: 10.1007/s15010-022-01855-2. Epub 2022 Jun 3.
PubMed 35657529Duval X, Taha MK, Lamaury I, Escaut L, Gueit I, Manchon P, Tubiana S, Hoen B; COMBAT study group. One-Year Sequelae and Quality of Life in Adults with Meningococcal Meningitis: Lessons from the COMBAT Multicentre Prospective Study. Adv Ther. 2022 Jun;39(6):3031-3041. doi: 10.1007/s12325-022-02149-7. Epub 2022 Apr 28.
PubMed 35484469Benadji A, Duval X, Danis K, Hoen B, Page B, Beraud G, Vernet-Garnier V, Strady C, Brieu N, Maulin L, Roy C, Ploy MC, Gaillat J, Varon E, Tubiana S; COMBAT Study Group; SIIP Study Group. Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease. Infection. 2022 Feb;50(1):223-233. doi: 10.1007/s15010-021-01688-5. Epub 2021 Sep 1.
PubMed 34468953Tubiana S, Varon E, Biron C, Ploy MC, Mourvillier B, Taha MK, Revest M, Poyart C, Martin-Blondel G, Lecuit M, Cua E, Pasquet B, Preau M, Hoen B, Duval X; COMBAT study group. Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort. Clin Microbiol Infect. 2020 Sep;26(9):1192-1200. doi: 10.1016/j.cmi.2019.12.020. Epub 2020 Jan 10.
PubMed 31927117
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bacterial Meningitis in Adults: Analysis of the Determinants of Mortality and Neurosensory Sequelae
- ClinicalTrials.gov ID
- NCT01730690
- Acronym / sponsor ID
- COMBAT / CRC11040
- Conditions
- Meningitis, Bacterial
- Keywords
- Bacterial meningitis in adults, determinants of in-hospital mortality
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 527 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 21 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with bacterial meningitis adults
Key inclusion criteria (4 listed)
- Positive CSF culture and/or positive soluble antigens in CSF with or without a cell reaction
- Positive PCR in CSF
- Purpura fulminant (with or without positive CSF culture)
- Positive PCR in blood and/or positive blood culture AND CSF cell reaction.
Key exclusion criteria (2 listed)
- Age less than 18 years old
- Refusal to participate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
In-hospital mortality
Time frame: 30 days
mortality in hospital at 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2017.
- Derived from this study: PubMed 42979101de Villiers de la Noue V, Tubiana S, Rontani M, Giry M, Sarton B, Pommier JD, Terzi N, Jozwiak M, Argaud L, Dupuis C, Marin N, Quenot JP, Nedelec P, Garcia M, Barbier F, Kuteifan K, Benchabane N, Duval X, Mourvillier B; COMBAT cohort study. Prognostic factors in ICU patients with community-acquired bacterial meningitis: A post hoc analysis of a multicenter prospective cohort study. J Intensive Med. 2026 Jun 13;6(5):524-533. doi: 10.1016/j.jointm.2026.04.007. eCollection 2026 Oct.
- Derived from this study: PubMed 37867184Van RN, Tubiana S, De Broucker T, Cedric J, Roy C, Meyohas MC, Prazuck T, Chirouze C, Hoen B, Duval X, Revest M; COMBAT study group. Persistent headaches one year after bacterial meningitis: prevalence, determinants and impact on quality of life. Eur J Clin Microbiol Infect Dis. 2023 Dec;42(12):1459-1467. doi: 10.1007/s10096-023-04673-y. Epub 2023 Oct 23.
- Derived from this study: PubMed 36952472Della Vecchia C, Ebah JV, Tubiana S, Guimard T, Piroth L, Jaffuel S, Gorenne I, Mourvillier B, Hoen B, Duval X, Preau M. Mid-term health-related quality of life in community-acquired bacterial meningitis survivors; the COMBAT study. PLoS One. 2023 Mar 23;18(3):e0281544. doi: 10.1371/journal.pone.0281544. eCollection 2023.
- Derived from this study: PubMed 35657529Akroum S, Tubiana S, de Broucker T, Dournon N, Varon E, Ploy MC, Mourvillier B, Oziol E, Lacassin F, Laurichesse H, Hoen B, Duval X, Burdet C; and the COMBAT study group. Long-term neuro-functional disability in adult patients with community-acquired bacterial meningitis. Infection. 2022 Oct;50(5):1363-1372. doi: 10.1007/s15010-022-01855-2. Epub 2022 Jun 3.
- Derived from this study: PubMed 35484469Duval X, Taha MK, Lamaury I, Escaut L, Gueit I, Manchon P, Tubiana S, Hoen B; COMBAT study group. One-Year Sequelae and Quality of Life in Adults with Meningococcal Meningitis: Lessons from the COMBAT Multicentre Prospective Study. Adv Ther. 2022 Jun;39(6):3031-3041. doi: 10.1007/s12325-022-02149-7. Epub 2022 Apr 28.
- Derived from this study: PubMed 34468953Benadji A, Duval X, Danis K, Hoen B, Page B, Beraud G, Vernet-Garnier V, Strady C, Brieu N, Maulin L, Roy C, Ploy MC, Gaillat J, Varon E, Tubiana S; COMBAT Study Group; SIIP Study Group. Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease. Infection. 2022 Feb;50(1):223-233. doi: 10.1007/s15010-021-01688-5. Epub 2021 Sep 1.
- Derived from this study: PubMed 31927117Tubiana S, Varon E, Biron C, Ploy MC, Mourvillier B, Taha MK, Revest M, Poyart C, Martin-Blondel G, Lecuit M, Cua E, Pasquet B, Preau M, Hoen B, Duval X; COMBAT study group. Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort. Clin Microbiol Infect. 2020 Sep;26(9):1192-1200. doi: 10.1016/j.cmi.2019.12.020. Epub 2020 Jan 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xavier duval principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Meningitis, Bacterial, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In-hospital mortality (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01730690, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2017.