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

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ClinicalTrials.gov Identifier: NCT04545164
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : September 17, 2020
Sponsor:
Collaborators:
Liverpool School of Tropical Medicine
University of Malawi College of Medicine
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Study Description
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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.


Condition or disease Intervention/treatment Phase
Tuberculosis Infection HIV Infections Diagnostic Test: CAD4TB Diagnostic Test: FujiLAM Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 690 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Computer Aided Screening for Tuberculosis in Low Resource Environments
Actual Study Start Date : September 2, 2020
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
No Intervention: Usual Care
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.
Experimental: DCXR-CAD and FujiLAM and usual care
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
CAD4TB is a Computer Aided Diagnosis (CAD) image processing algorithm that can aid interpretation of Chest X-ray images to accurately detect tuberculosis.

Diagnostic Test: FujiLAM
Fujifilm SILVAMP TB LAM is a high sensitivity test for mycobacterial lipoarabinomannan (LAM) in urine samples.
Diagnostic cohort
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
CAD4TB is a Computer Aided Diagnosis (CAD) image processing algorithm that can aid interpretation of Chest X-ray images to accurately detect tuberculosis.

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


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04545164


Contacts
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Contact: Rachael M Burke +265 1811628 rachael.burke@lshtm.ac.uk

Locations
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Malawi
Zomba Central Hospital Recruiting
Zomba, Malawi
Contact: Rachael Burke       rachael.burke@lshtm.ac.uk   
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Liverpool School of Tropical Medicine
University of Malawi College of Medicine
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Investigators
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Principal Investigator: Rachael M Burke London School of Hygiene and Tropical Medicine
More Information
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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT04545164    
Other Study ID Numbers: 17799
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: September 17, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD will be shared on LSHTM Data Compass.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Tuberculosis
Latent Tuberculosis
Disease Attributes
Pathologic Processes
 Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Latent Infection