Computer Aided Screening for Tuberculosis in Low Resource Environments

NCT04545164 | Completed DMC

• 1 other identifier: 17799
• Study Type: interventional
• Target: 498
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis Infection; HIV Infections

Outcome Measures

Primary Outcomes (1)

• TB treatment initiation

  Proportion of participants started on TB treatment

  From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)

Secondary Outcomes (3)

• Mortality

  Censored at 56 days from enrolment

• Undiagnosed TB

  From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)

• Same day TB treatment

  24 hours from enrolment

Other Outcomes (6)

• Mortality (measured as a proportion)

  56 days from enrolment

• Inpatient mortality

  Censored at 56 days for those who are still alive and admitted to hospital at 56 days from enrolment.

• Confirmed TB

  From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)

Study Arms (3)

Usual Care

NO INTERVENTION

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

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 Test: CAD4TB; Diagnostic Test: FujiLAM

Diagnostic cohort

OTHER

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 Test: CAD4TB; Diagnostic Test: FujiLAM

Interventions

CAD4TB DIAGNOSTIC_TEST

CAD4TB is a Computer Aided Diagnosis (CAD) image processing algorithm that can aid interpretation of Chest X-ray images to accurately detect tuberculosis.

DCXR-CAD and FujiLAM and usual care; Diagnostic cohort

FujiLAM DIAGNOSTIC_TEST

Fujifilm SILVAMP TB LAM is a high sensitivity test for mycobacterial lipoarabinomannan (LAM) in urine samples.

DCXR-CAD and FujiLAM and usual care; Diagnostic cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Liverpool School of Tropical Medicine: collaborator
• Kamuzu University of Health Sciences: collaborator
• Malawi-Liverpool-Wellcome Trust Clinical Research Programme: collaborator

Study Sites (1)

Zomba Central Hospital

Zomba, Malawi

Location

Related Publications (1)

• 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.

  PMID: 35007306 BACKGROUND

MeSH Terms

Conditions

Latent Tuberculosis; HIV Infections

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Rachael M Burke

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: September 10, 2020
• Study Start: September 2, 2020
• Primary Completion: March 31, 2022
• Study Completion: May 26, 2022
• Last Updated: January 26, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

MA (1)