NCT04190303

Brief 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. 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,233

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Feb 2021

Geographic Reach
3 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 1, 2019

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 9, 2019

Completed
1.2 years until next milestone

Study Start

First participant enrolled

February 17, 2021

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2022

Completed
Last Updated

March 3, 2025

Status Verified

February 1, 2025

Enrollment Period

1.9 years

First QC Date

December 1, 2019

Last Update Submit

February 26, 2025

Conditions

MeningitisEncephalitisAbscess Brain

Outcome Measures

Primary Outcomes (2)

  • Microbiological diagnosis

    Proportion of patients achieving microbiological diagnosis

    During hospital admission, or at 30 days if participant still in hospital

  • Syndromic diagnosis

    Proportion of patients achieving syndromic diagnosis

    During hospital admission, or at 30 days if participant still in hospital

Secondary Outcomes (10)

  • Proportion receiving, and time to lumbar puncture

    During hospital admission, or at 30 days if participant still in hospital

  • Proportion having appropriate cerebrospinal fluid investigations

    During hospital admission, or at 30 days if participant still in hospital

  • Mortality

    At 30 days

  • Length of stay in hospital

    During hospital admission, or at 30 days if participant still in hospital

  • Time to appropriate empirical therapy

    During hospital admission, or at 30 days if participant still in hospital

  • +5 more secondary outcomes

Study Arms (2)

Baseline (pre-intervention)

Current routine care

Post-intervention

Care following development and delivery of the system-level intervention

Other: Pragmatic, multi-component package

Interventions

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

Post-intervention

Eligibility Criteria

Age4 Weeks+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Patients presenting to a study hospital with symptoms and/or signs suggestive of an acute brain infection.

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

FioCruz

Recife, Brazil

Location

National Institute of Mental Health and Neurosciences

Bangalore, India

Location

Christian Medical College

Vellore, India

Location

Malawi Liverpool Wellcome Trust

Blantyre, Malawi

Location

Related Publications (1)

  • 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.

    PMID: 40081400DERIVED

MeSH Terms

Conditions

MeningitisEncephalitisBrain Abscess

Condition Hierarchy (Ancestors)

Neuroinflammatory DiseasesNervous System DiseasesBrain DiseasesCentral Nervous System DiseasesCentral Nervous System InfectionsInfectionsAbscessSuppuration

Study Officials

  • Tom Solomon, PhD

    Institute of Infection & Global Health, University of Liverpool

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

December 1, 2019

First Posted

December 9, 2019

Study Start

February 17, 2021

Primary Completion

December 31, 2022

Study Completion

December 31, 2022

Last Updated

March 3, 2025

Record last verified: 2025-02

Locations

IN(2)BR(1)MA(1)