Computer Aided Screening for Tuberculosis in Low Resource Environments

Not Applicable

Completed

• Conditions: HIV Infections; Tuberculosis Infection
• Interventions: Diagnostic Test: CAD4TB; Diagnostic Test: FujiLAM

• Registration Number: NCT04545164
• Lead Sponsor: London School of Hygiene and Tropical Medicine

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

Study Timeline

• Study First Submitted: 2020-09-01
• Study Start: 2020-09-02
• Study First Submitted QC: 2020-09-07
• Study First Posted: 2020-09-10
• Primary Completion: 2022-03-31
• Status Verified: 2022-05
• Study Completion: 2022-05-26
• Last Update Submitted: 2023-01-23
• Last Update Posted: 2023-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 498

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DCXR-CAD and FujiLAM and usual care	FujiLAM	Participants randomized to the intervention arm will receive TB screening using DCXR-CAD and urine FujiLAM. The CAD score and FujLAM results will be appended into their medical notes for treating clinicians to see. If patients have a CAD score above a pre-determined threshold the study team will attempt to collect sputum for Xpert Mtb/Rif. Chest X-ray images will be available for clinicians to view. This is in addition to usual care (detailed above).
Diagnostic cohort	FujiLAM	Patients in the observational enhanced diagnostic arm will receive an enhanced package of diagnostics. This is a smaller arm (1 in 9 of all clusters) and is observational only - participants in this arm do not contribute to trial outcomes.
Diagnostic cohort	CAD4TB	Patients in the observational enhanced diagnostic arm will receive an enhanced package of diagnostics. This is a smaller arm (1 in 9 of all clusters) and is observational only - participants in this arm do not contribute to trial outcomes.
DCXR-CAD and FujiLAM and usual care	CAD4TB	Participants randomized to the intervention arm will receive TB screening using DCXR-CAD and urine FujiLAM. The CAD score and FujLAM results will be appended into their medical notes for treating clinicians to see. If patients have a CAD score above a pre-determined threshold the study team will attempt to collect sputum for Xpert Mtb/Rif. Chest X-ray images will be available for clinicians to view. This is in addition to usual care (detailed above).

Primary Outcome Measures

Name	Time	Method
TB treatment initiation	From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)	Proportion of participants started on TB treatment

Secondary Outcome Measures

Name	Time	Method
Same day TB treatment	24 hours from enrolment	Proportion of people starting TB treatment within 24 hours of enrollment
Undiagnosed TB	From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)	Positive sputum culture for mycobacterium tuberculosis at reference lab and participant is not on TB treatment at time of hospital discharge or death.
Mortality	Censored at 56 days from enrolment	Time (in days) to death from any case.

Trial Locations

Locations (1)

Zomba Central Hospital; 🇲🇼 Zomba, Malawi