Computer Aided Screening for Tuberculosis in Low Resource Environments (CASTLE)

London School of Hygiene and Tropical Medicine

Status: Completed

Conditions: Tuberculosis Infection; HIV Infections

Treatments: Diagnostic Test: FujiLAM; Diagnostic Test: CAD4TB

Study type: Interventional

Funder types: Other

Identifiers

NCT04545164

17799

Details and patient eligibility

About

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.

Full description

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

Enrollment: 498 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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498 participants in 3 patient groups

Usual Care

No Intervention group

Description:

Participants in the usual care arm will receive no specific trial intervention. Usual care includes tests routinely available at Zomba Central Hospital, including (but not limited to) conventional (plain film) chest X-ray, urine Alere LAM and sputum Xpert Mtb/Rif on treating clinician request.

DCXR-CAD and FujiLAM and usual care

Experimental group

Description:

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).

Treatment:

Diagnostic Test: CAD4TB

Diagnostic Test: FujiLAM

Diagnostic cohort

Other group

Description:

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.

Treatment:

Diagnostic Test: CAD4TB

Diagnostic Test: FujiLAM