BIGlobal Intervention Study: Improving Diagnosis and Management of Suspected Brain Infections Globally

• ClinicalTrials.gov Identifier: NCT04190303
• Recruitment Status: Recruiting
• First Posted: December 9, 2019
• Last Update Posted: October 1, 2021
• Sponsor: University of Liverpool
• 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
• Information provided by (Responsible Party): Tom Solomon, University of Liverpool

Tracking Information

• First Submitted Date: December 1, 2019
• First Posted Date: December 9, 2019
• Last Update Posted Date: October 1, 2021
• Actual Study Start Date: February 17, 2021
• Estimated Primary Completion Date: March 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 4, 2019)

• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 4, 2019)

• Proportion receiving, and time to lumbar puncture [ Time Frame: During hospital admission, or at 30 days if participant still in hospital ]
  Proportion of study participants receiving a lumbar puncture, and time to lumbar puncture
• Proportion having appropriate cerebrospinal fluid investigations [ Time Frame: During hospital admission, or at 30 days if participant still in hospital ]
  All of: cell count, total and differential; CSF protein concentration; CSF glucose concentration; paired serum/blood glucose concentration; microscopy and culture for bacteria
• Mortality [ Time Frame: At 30 days ]
  All-cause
• Length of stay in hospital [ Time Frame: During hospital admission, or at 30 days if participant still in hospital ]
  Duration of hospital admission
• Time to appropriate empirical therapy [ Time Frame: During hospital admission, or at 30 days if participant still in hospital ]
  Time to appropriate empirical anti-infective therapy
• Time to appropriate definitive therapy [ Time Frame: During hospital admission, or at 30 days if participant still in hospital ]
  Time to appropriate definitive anti-infective therapy
• Quality of life score [ Time Frame: At hospital discharge, or at 30 days if participant still in hospital ]
  Using EuroQol EQ-5D questionnaires scoring 5 domains at levels 1-3 each, and an overall health state from 0 to 100.
• Quality of life score [ Time Frame: At 30 days after presentation to hospital ]
  Using EuroQol EQ-5D questionnaires scoring 5 domains at levels 1-3 each, and an overall health state from 0 to 100.
• Liverpool Outcome Score [ Time Frame: At hospital discharge, or at 30 days if participant still in hospital ]
  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.
• Liverpool Outcome Score [ Time Frame: At 30 days after presentation to hospital ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: BIGlobal Intervention Study: Improving Diagnosis and Management of Suspected Brain Infections Globally
• 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

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.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample
• Study Population: Patients presenting to a study hospital with symptoms and/or signs suggestive of an acute brain infection.

Condition

• Meningitis
• Encephalitis
• Abscess Brain

Intervention

Other: Pragmatic, multi-component package

This system-level intervention will be tailored to the needs and capacity of each hospital site, co-developed with policymakers and hospital staff

Study Groups/Cohorts

• Baseline (pre-intervention)
  Current routine care
• Post-intervention
  Care following development and delivery of the system-level intervention
  Intervention: Other: Pragmatic, multi-component package

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 4, 2019): 3600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2022
• Estimated Primary Completion Date: March 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 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.
2. Symptom duration of less than 4 weeks.

Exclusion Criteria:

1. Neonates, i.e. children under the age of 28 days.
2. 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).
3. People without an indwelling device, having undergone neurosurgical procedures within the preceding 12 months.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Weeks and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Bhagteshwar Singh, MBChB; +441517957577; bsingh@liverpool.ac.uk

• Listed Location Countries: Brazil, India, Malawi

Administrative Information

• NCT Number: NCT04190303
• Other Study ID Numbers: UoL001430 - 4069
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Tom Solomon, University of Liverpool
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Liverpool
• Original Study Sponsor: Same as current

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

Investigators

• Principal Investigator: Tom Solomon, PhD; Institute of Infection & Global Health, University of Liverpool

• PRS Account: University of Liverpool
• Verification Date: September 2021