Clinical trial NCT04545164: Computer Aided Screening for Tuberculosis in Low Resource Environments
Official title: Computer Aided Screening for Tuberculosis in Low Resource Environments
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis Infection
HIV Infections
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Liverpool School of Tropical Medicine
name: Kamuzu University of Health Sciences
name: Malawi-Liverpool-Wellcome Trust Clinical Research Programme
First posted: 2020-09-10
Enrollment: 498
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: People living with HIV (PLHIV) who require admission to hospital in WHO Africa region have poor outcomes. TB is very common in this group, but can be difficult to diagnose.

The CASTLE trial aims to determine whether systematic screening for tuberculosis using digital chest X-ray with computer-aided diagnosis (DCXR-CAD) plus urine lipoarabinomannan testing with Fujifilm SILVAMP TB LAM (FujiLAM) plus usual care can improve admission outcomes for hospitalised PLHIV, compared to usual care alone.

Our study is a single centre, unblinded, cluster-randomised (by day of admission) trial of DCXR-CAD plus FujiLAM plus usual care vs. usual care alone for screening for TB in unselected adult PLHIV admitted to a district general hospital in Malawi.

The primary outcome is the proportion of people starting TB treatment by the time of death or hospital discharge. The secondary outcomes are all-cause mortality at 56 days from enrolment, proportion of people starting TB treatment within 24 hours from enrolment, and proportion of people with undiagnosed TB. In the CASTLE study we collect a single sputum sample for M. tb culture from participants and undiagnosed TB specifically refers to a person who did not start TB treatment by the time of death or discharge from hospital and has a M. tb cultured from their sputum sample.

Alongside the two trial arms, a third smaller diagnostic cohort arm (1 in 9 of admission days / trial clusters) will explore the range of underlying infectious pathology. The diagnostic cohort does not contribute to trial outcomes.

Detailed description: CASTLE is funded by Wellcome, grant reference 203905/Z/16/Z

Eligibility criteria: Inclusion Criteria:

* Requires acute admission to a hospital medical ward at Zomba Central Hospital for any reason
* Is living with HIV (existing or new diagnosis, irrespective of ART status)
* Willing and able to give informed consent

Exclusion Criteria:

* Aged \<18 years
* Has been admitted to a medical ward for longer than 18 hours
* Taking TB treatment before admission or has received treatment for TB within the preceding 6 months.
* Has already been in the study during an earlier hospital admission.

Primary outcomes:
measure: TB treatment initiation
timeFrame: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Secondary outcomes:
measure: Mortality
timeFrame: Censored at 56 days from enrolment
measure: Undiagnosed TB
timeFrame: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
measure: Same day TB treatment
timeFrame: 24 hours from enrolment
Other outcomes:
measure: Mortality (measured as a proportion)
timeFrame: 56 days from enrolment
measure: Inpatient mortality
timeFrame: Censored at 56 days for those who are still alive and admitted to hospital at 56 days from enrolment.
measure: Confirmed TB
timeFrame: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
measure: Intervention fidelity
timeFrame: 24 hours from enrolment
measure: Diagnostic accuracy of DCXR-CAD
timeFrame: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
measure: Prevalence of infectious disease (enhanced diagnostic cohort)
timeFrame: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Locations:
city: Zomba
country: Malawi
facility: Zomba Central Hospital
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Rachael M Burke
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burke RM, Nyirenda S, Twabi HH, Nliwasa M, Joekes E, Walker N, Nyirenda R, Gupta-Wright A, Fielding K, MacPherson P, Corbett EL. Design and protocol for a cluster randomised trial of enhanced diagnostics for tuberculosis screening among people living with HIV in hospital in Malawi (CASTLE study). PLoS One. 2022 Jan 10;17(1):e0261877. doi: 10.1371/journal.pone.0261877. eCollection 2022.