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Completed

NCT Number: NCT04545164

Computer Aided Screening for Tuberculosis in Low Resource Environments

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Zomba Central Hospital

Zomba, Malawi

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

FujiLAM

Diagnostic Test

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

Primary outcomes

  1. TB treatment initiation

    Time frame: 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 outcomes

  1. Mortality

    Time frame: Censored at 56 days from enrolment

    Time (in days) to death from any case.

  2. Undiagnosed TB

    Time frame: 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.

  3. Same day TB treatment

    Time frame: 24 hours from enrolment

    Proportion of people starting TB treatment within 24 hours of enrollment

Other outcomes

  1. Mortality (measured as a proportion)

    Time frame: 56 days from enrolment

    Proportion of people dying by 56 days from enrolment.

  2. Inpatient mortality

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

    Proportion of people dying prior to hospital discharge

  3. Confirmed TB

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

    The proportion of TB diagnoses that are microbiologically confirmed vs. clinically diagnosed without microbiological confirmation.

  4. Intervention fidelity

    Time frame: 24 hours from enrolment

    Proportion of people randomised to DCXR-CAD plus FujiLAM who have a valid CxR and CAD score recorded, and a FujiLAM result.

  5. Diagnostic accuracy of DCXR-CAD

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

    Sensitivity, specificity, positive and negative predictor value compared to a composite microbiological gold standard.

  6. Prevalence of infectious disease (enhanced diagnostic cohort)

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

    To describe the proportion of patients meeting a clinical or clinical / microbiological description for the following: Sepsis; Invasive bacterial disease; Cryptococcal disease; Pneumocystis jirovecci pneumonia; Bacterial pneumonia; Immune reconstitution inflammatory syndrome (IRIS); HIV treatment failure

Sponsors and collaborators

Lead sponsor

London School of Hygiene and Tropical Medicine

Other

Collaborators

  • Kamuzu University of Health Sciences
  • Liverpool School of Tropical Medicine
  • Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Registry information

Acronym: CASTLE

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Sep 10, 2020
Registry last updated
Jan 26, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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