Computer Aided Screening for Tuberculosis in Low Resource Environments

HIV Infections Clinical Trial

— CASTLE  

Official title:

Computer Aided Screening for Tuberculosis in Low Resource Environments

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04545164
• Other study ID #: 17799
• Status: Completed
• Phase: N/A
• Start date: September 2, 2020
• Est. completion date: May 26, 2022

Study information

• Verified date: May 2022
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 498
• Est. completion date: May 26, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infections
• Latent Tuberculosis
• Tuberculosis
• Tuberculosis Infection

Intervention

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

Locations

Country	Name	City	State
Malawi	Zomba Central Hospital	Zomba

Sponsors (4)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Kamuzu University of Health Sciences, Liverpool School of Tropical Medicine, Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Country where clinical trial is conducted

Malawi, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality (measured as a proportion)	Proportion of people dying by 56 days from enrolment.	56 days from enrolment
Other	Inpatient mortality	Proportion of people dying prior to hospital discharge	Censored at 56 days for those who are still alive and admitted to hospital at 56 days from enrolment.
Other	Confirmed TB	The proportion of TB diagnoses that are microbiologically confirmed vs. clinically diagnosed without microbiological confirmation.	From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Other	Intervention fidelity	Proportion of people randomised to DCXR-CAD plus FujiLAM who have a valid CxR and CAD score recorded, and a FujiLAM result.	24 hours from enrolment
Other	Diagnostic accuracy of DCXR-CAD	Sensitivity, specificity, positive and negative predictor value compared to a composite microbiological gold standard.	From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Other	Prevalence of infectious disease (enhanced diagnostic cohort)	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	From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Primary	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	Mortality	Time (in days) to death from any case.	Censored at 56 days from enrolment
Secondary	Undiagnosed TB	Positive sputum culture for mycobacterium tuberculosis at reference lab and participant is not on TB treatment at time of hospital discharge or death.	From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Secondary	Same day TB treatment	Proportion of people starting TB treatment within 24 hours of enrollment	24 hours from enrolment