MeningitisNCT04190303
BIGlobal Intervention Study: Improving Diagnosis and Management of Suspected Brain Infections Globally
An observational study of Meningitis and Encephalitis, run by University of Liverpool at 4 sites in 3 countries.
Trial summary
Background: Patients with suspected brain infections pose major challenges to low and middle income countries, including their disproportionately high burden, diverse causes with inadequate surveillance, requirement for invasive and expensive tests, and the difficulty of management without a clear diagnosis. Read more about this study
- Who is it for?
- Ages 4 weeks and older
- Conditions the study is for
- Meningitis, Encephalitis, Abscess Brain
- What is being tested?
- Pragmatic, multi-component package
- How many people
- 2,233 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 17 Feb 2021to 31 Dec 2022
- 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 4 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients presenting to a study hospital with symptoms and/or signs suggestive of an acute brain infection.
Who may be able to join
- Adults, infants and children presenting to a study hospital with symptoms and/or signs suggestive of acute brain infection, which could be suspected encephalitis, suspected meningitis, or alternative features raising suspicion of brain infection.
- Symptom duration of less than 4 weeks.
Who cannot join
- Neonates, i.e. children under the age of 28 days.
- People with pre-existing indwelling ventricular devices (e.g. extra-ventricular drains, ventriculo-peritoneal shunts) or other implants in contact with the meninges or brain (e.g. deep brain stimulators).
- People without an indwelling device, having undergone neurosurgical procedures within the preceding 12 months.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
India2 sites
National Institute of Mental Health and Neurosciences
Bangalore
Christian Medical College
Vellore
About this study
Official title: NIHR Global Health Research Group on Brain Infections Study: Establishing a Standard Care Package to Improve Diagnosis and Early Hospital Management of Patients With Suspected Acute Brain Infections in Low and Middle Income Countries
Background: Patients with suspected brain infections pose major challenges to low and middle income countries, including their disproportionately high burden, diverse causes with inadequate surveillance, requirement for invasive and expensive tests, and the difficulty of management without a clear diagnosis. This is all compounded by resource and system constraints. Few studies have attempted to improve the care of these people in resource-limited settings.
Aim: This study sets out to improve the diagnosis and early management of people with suspected acute (<28 days of symptoms) brain infections in low and middle income countries, using a coordinated thematic approach.
Read more
Outcomes: The primary outcome will be proportion of people with suspected acute brain infection receiving a diagnosis. Secondary outcomes will include mortality, length of stay in hospital, quality of life, degree of disability, and proportion having a lumbar puncture test.
Participants: Children and adults with features consistent with an acute brain infection, including meningitis and encephalitis, will be recruited at a variety of hospitals in Brazil, India and Malawi.
Study procedures: An assessment of current practice and capabilities at each hospital, including patient and sample journey observations and interviews with healthcare staff, will identify barriers to optimal care. Using this, a sustainable pragmatic multi-component intervention will be produced, with components modifiable to each hospital's needs. Outcomes will be reassessed post-intervention.
- Conditions
- Meningitis, Encephalitis, Abscess Brain
- Being tested
- Pragmatic, multi-component package
- Medical subject headings
- Meningitis, Encephalitis, Brain Abscess
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pragmatic, multi-component packageOther
This system-level intervention will be tailored to the needs and capacity of each hospital site, co-developed with policymakers and hospital staff
| Study group | Role | What they receive |
|---|---|---|
| Baseline (pre-intervention) | Current routine care | |
| Post-intervention | Care following development and delivery of the system-level intervention Receives: Other: Pragmatic, multi-component package |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microbiological diagnosis
Proportion of patients achieving microbiological diagnosis
Measured: During hospital admission, or at 30 days if participant still in hospital
Syndromic diagnosis
Proportion of patients achieving syndromic diagnosis
Measured: During hospital admission, or at 30 days if participant still in hospital
Secondary outcomes (10)
Proportion receiving, and time to lumbar puncture
Proportion of study participants receiving a lumbar puncture, and time to lumbar puncture
Measured: During hospital admission, or at 30 days if participant still in hospital
Proportion having appropriate cerebrospinal fluid investigations
All of: cell count, total and differential; CSF protein concentration; CSF glucose concentration; paired serum/blood glucose concentration; microscopy and culture for bacteria
Measured: During hospital admission, or at 30 days if participant still in hospital
Mortality
All-cause
Measured: At 30 days
Length of stay in hospital
Duration of hospital admission
Measured: During hospital admission, or at 30 days if participant still in hospital
Time to appropriate empirical therapy
Time to appropriate empirical anti-infective therapy
Measured: During hospital admission, or at 30 days if participant still in hospital
Time to appropriate definitive therapy
Time to appropriate definitive anti-infective therapy
Measured: During hospital admission, or at 30 days if participant still in hospital
Quality of life score
Using EuroQol EQ-5D questionnaires scoring 5 domains at levels 1-3 each, and an overall health state from 0 to 100.
Measured: At hospital discharge, or at 30 days if participant still in hospital
Quality of life score
Using EuroQol EQ-5D questionnaires scoring 5 domains at levels 1-3 each, and an overall health state from 0 to 100.
Measured: At 30 days after presentation to hospital
Liverpool Outcome Score
Score measuring neurological function after brain infection, reporting a lowest score of 15 domains between 2 and 5, and a total score with range 33-75.
Measured: At hospital discharge, or at 30 days if participant still in hospital
Liverpool Outcome Score
Score measuring neurological function after brain infection, reporting a lowest score of 15 domains between 2 and 5, and a total score with range 33-75.
Measured: At 30 days after presentation to hospital
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2019
- Study start17 Feb 2021
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MeningitisStudies of the same condition, open and under way.
- 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
- Other
- Time perspective
- Prospective
- Enrolment
- 2,233 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Christian Medical College, Vellore, India, National Institute of Mental Health and Neuro Sciences, India, Oswaldo Cruz Foundation, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, University of Warwick, Liverpool School of Tropical Medicine
- Responsible party
- Principal investigator, Tom Solomon, University of Liverpool
- Investigators
- Tom Solomon, PhD, Principal investigator, Institute of Infection & Global Health, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04190303
- Sponsor's protocol ID
- UoL001430 - 4069
- Status last verified
- Feb 2025
- First submitted
- 1 Dec 2019
- Last updated
- 3 Mar 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Singh B, Lipunga GD, Thangavelu P, Dhar S, Ferreira Cronemberger L, Abhilash KPP, Abraham AM, de Brito CAA, Brito Ferreira ML, Chandrashekar N, Duarte R, Fajardo Modol A, Ghale BC, Kang G, Gowda VK, Kuriakose K, Lant S, Mallewa M, Mbale E, Moore SC, Mwangalika G, Kamath PBT, Navvuga P, Nyondo-Mipando AL, Phiri TJ, Pimentel Lopes de Melo C, Pradeep BS, Rawlinson R, Sheha I, Thomas PT, Newton CR, de Sequeira PC, Sejvar JJ, Dua T, Turtle L, Verghese VP, Arraes LWMS, Desmond N, Easton A, Jones JA, Lilford RJ, Netravathi M, McGill F, Michael BD, Mwapasa V, Griffiths MJ, Parry CM, Ravi V, Burnside G; Brain Infections Global Intervention Study Group; Cornick J, Franca RFO, Desai AS, Rupali P, Solomon T. A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study. Lancet. 2025 Mar 22;405(10483):991-1003. doi: 10.1016/S0140-6736(25)00263-6. Epub 2025 Mar 10.
PubMed 40081400
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NIHR Global Health Research Group on Brain Infections Study: Establishing a Standard Care Package to Improve Diagnosis and Early Hospital Management of Patients With Suspected Acute Brain Infections in Low and Middle Income Countries
- ClinicalTrials.gov ID
- NCT04190303
- Acronym / sponsor ID
- UoL001430 - 4069
- Conditions
- Meningitis, Encephalitis, Abscess Brain
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,233 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Christian Medical College, Vellore, India, National Institute of Mental Health and Neuro Sciences, India, Oswaldo Cruz Foundation, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, University of Warwick, Liverpool School of Tropical Medicine
- Study start
- 17 Feb 2021 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 9 Dec 2019 (actual)
- 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.
Background: Patients with suspected brain infections pose major challenges to low and middle income countries, including their disproportionately high burden, diverse causes with inadequate surveillance, requirement for invasive and expensive tests, and the difficulty of management without a clear diagnosis. This is all compounded by resource and system constraints. Few studies have attempted to improve the care of these people in resource-limited settings.
Aim: This study sets out to improve the diagnosis and early management of people with suspected acute (<28 days of symptoms) brain infections in low and middle income countries, using a coordinated thematic approach.
Outcomes: The primary outcome will be proportion of people with suspected acute brain infection receiving a diagnosis. Secondary outcomes will include mortality, length of stay in hospital, quality of life, degree of disability, and proportion having a lumbar puncture test.
Participants: Children and adults with features consistent with an acute brain infection, including meningitis and encephalitis, will be recruited at a variety of hospitals in Brazil, India and Malawi.
Study procedures: An assessment of current practice and capabilities at each hospital, including patient and sample journey observations and interviews with healthcare staff, will identify barriers to optimal care. Using this, a sustainable pragmatic multi-component intervention will be produced, with components modifiable to each hospital's needs. Outcomes will be reassessed post-intervention.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Baseline (pre-intervention) | – | –Current routine care |
| Post-intervention | – | Other: Pragmatic, multi-component packageCare following development and delivery of the system-level intervention |
Who may qualify
- Ages
- 4 weeks and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients presenting to a study hospital with symptoms and/or signs suggestive of an acute brain infection.
Key inclusion criteria (2 listed)
- Adults, infants and children presenting to a study hospital with symptoms and/or signs suggestive of acute brain infection, which could be suspected encephalitis, suspected meningitis, or alternative features raising suspicion of brain infection.
- Symptom duration of less than 4 weeks.
Key exclusion criteria (3 listed)
- Neonates, i.e. children under the age of 28 days.
- People with pre-existing indwelling ventricular devices (e.g. extra-ventricular drains, ventriculo-peritoneal shunts) or other implants in contact with the meninges or brain (e.g. deep brain stimulators).
- People without an indwelling device, having undergone neurosurgical procedures within the preceding 12 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pragmatic, multi-component packageThis system-level intervention will be tailored to the needs and capacity of each hospital site, co-developed with policymakers and hospital staff | Other | Post-intervention |
Primary outcome
Microbiological diagnosis
Time frame: During hospital admission, or at 30 days if participant still in hospital
Proportion of patients achieving microbiological diagnosis
Syndromic diagnosis
Time frame: During hospital admission, or at 30 days if participant still in hospital
Proportion of patients achieving syndromic diagnosis
10 secondary outcomes
Proportion receiving, and time to lumbar puncture
Time frame: During hospital admission, or at 30 days if participant still in hospital
Proportion having appropriate cerebrospinal fluid investigations
Time frame: During hospital admission, or at 30 days if participant still in hospital
Mortality
Time frame: At 30 days
Length of stay in hospital
Time frame: During hospital admission, or at 30 days if participant still in hospital
Time to appropriate empirical therapy
Time frame: During hospital admission, or at 30 days if participant still in hospital
Time to appropriate definitive therapy
Time frame: During hospital admission, or at 30 days if participant still in hospital
Quality of life score
Time frame: At hospital discharge, or at 30 days if participant still in hospital
Quality of life score
Time frame: At 30 days after presentation to hospital
Liverpool Outcome Score
Time frame: At hospital discharge, or at 30 days if participant still in hospital
Liverpool Outcome Score
Time frame: At 30 days after presentation to hospital
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 3 Mar 2025.
- Derived from this study: PubMed 40081400Singh B, Lipunga GD, Thangavelu P, Dhar S, Ferreira Cronemberger L, Abhilash KPP, Abraham AM, de Brito CAA, Brito Ferreira ML, Chandrashekar N, Duarte R, Fajardo Modol A, Ghale BC, Kang G, Gowda VK, Kuriakose K, Lant S, Mallewa M, Mbale E, Moore SC, Mwangalika G, Kamath PBT, Navvuga P, Nyondo-Mipando AL, Phiri TJ, Pimentel Lopes de Melo C, Pradeep BS, Rawlinson R, Sheha I, Thomas PT, Newton CR, de Sequeira PC, Sejvar JJ, Dua T, Turtle L, Verghese VP, Arraes LWMS, Desmond N, Easton A, Jones JA, Lilford RJ, Netravathi M, McGill F, Michael BD, Mwapasa V, Griffiths MJ, Parry CM, Ravi V, Burnside G; Brain Infections Global Intervention Study Group; Cornick J, Franca RFO, Desai AS, Rupali P, Solomon T. A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study. Lancet. 2025 Mar 22;405(10483):991-1003. doi: 10.1016/S0140-6736(25)00263-6. Epub 2025 Mar 10.
- Individual participant dataSharing planned: Undecided
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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.
Tom Solomon, PhD principal investigator
Institute of Infection & Global Health, University of Liverpool
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Meningitis and Encephalitis, run by University of Liverpool at 4 sites in 3 countries.
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 2 inclusion and 3 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 3 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in India, Brazil, Malawi. 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?
Microbiological diagnosis (time frame: During hospital admission, or at 30 days if participant still in hospital). The study lists 2 primary outcomes in all. 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 NCT04190303, which also lists 1 linked publication.
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 3 Mar 2025.