Evaluating the Impact of Computer-assisted X-ray Diagnosis and Other Triage Tools to Optimise Xpert Orientated Community-based Active Case Finding for TB and COVID-19

NCT05220163 | Active Not Recruiting DMC

• 1 other identifier: XACT-19
• Study Type: interventional
• Target: 26,200
• Locations: 2 countries
• Sites: 2

Brief Summary

Tuberculosis (TB) is now the commonest cause of death in many African countries. Globally, \~35% (almost 1 in 3) of TB cases are 'missed' (remain undiagnosed or undetected). In sub-Saharan Africa, 40-50% of the TB case burden remains undiagnosed within the community. These 'missed' TB cases (at primary care level) serve as a reservoir, which severely undermines TB control. With rapid advances in the development of TB screening tests, the investigators aim to determine the pragmatic utility of computer-assisted x-ray diagnosis (CAD). Recent data suggest that CAD performs on par with experienced radiologists to identify potential TB cases, hereby reducing the frequency at which Xpert tests are requested and helps to focus limited resources on the relevant cases. In addition, the investigators aim to test nascent screening technologies for TB diagnosis such as evaluating urine-based TB screening biosignatures. The COVID-19 pandemic has ravaged African peri-urban communities where TB is also common. With the pressing need to improve screening and diagnosis of COVID-19, the investigators plan to explore the potential for urine- and blood-based COVID-19 screening assays. Symptoms of COVID-19 and TB overlap, and limited affordability, as well as the stigma associated with both diseases, severely limits testing. Data are now urgently needed about the feasibility of co-screening and testing for TB and COVID-19. The utility of such an approach, if any, has not been studied in African communities.

Conditions

Tuberculosis; COVID-19; HIV Infections

Keywords

Tuberculosis; Active case finding; Computer assisted diagnosis; Screening; COVID-19

Outcome Measures

Primary Outcomes (1)

• Time to detection of microbiologically proven TB

  The microbiological reference standard for TB will be culture and/or Xpert positivity. Thus, the overall time to detection (using a proportional hazards model) and the proportion of TB cases detected at a specific time-point (e.g., 14-, 30- and 60-days) with and without culture (Xpert alone) will be reported.

  Through study completion, up to 48 months

Secondary Outcomes (15)

• Feasibility of CAD + POC Xpert performed by minimally trained healthcare workers

  Through study completion, up to 48 months

• Number of infectious TB cases detected (defined by cough aerosol sampling system [CASS] and/or smear and/or cavitatory disease positive)

  Through study completion, up to 48 months

• Time-specific proportion of participants initiated on TB treatment up to 60 days post-sample donation in each arm (7-, 14-, 30- and 60-days)

  Through study completion, up to 48 months

• Time to TB treatment initiation (both the median time to treatment in each group and time to event [treatment] analyses will be conducted)

  Through study completion, up to 48 months

• Yield of culture positive TB in household contacts of index participants

  Through study completion, up to 48 months

Other Outcomes (3)

• Economic outcome: Cost effectiveness of CAD + POC Xpert (cost per TB case diagnosed and/or averted, and cost per death and disability-adjusted life year [DALY] averted)

  Through study completion, up to 48 months

• Economic outcome: Direct comparison of the cost effectiveness of ACF compared to passive case finding (the current public health practice)

  Through study completion, up to 48 months

• Economic outcome: Cost effectiveness considering drug resistant TB (DR-TB) and HIV prevention

  Through study completion, up to 48 months

Study Arms (2)

CAD + POC Xpert

EXPERIMENTAL

CAD followed by Xpert in CAD-positive participants (performed at POC) employing a low-cost panel van that is staffed by three health care workers. CAD-negative participants will be followed up, while CAD-positive participants will be offered POC Xpert. Xpert-positive participants will be referred for TB treatment initiation, while Xpert-negative (but CAD-positive) participants will undergo a clinical review. Thus, the active case finding (ACF) interventional package is one of CAD + POC Xpert (only in CAD positive participants).

Diagnostic Test: CAD; Diagnostic Test: Xpert

POC Xpert only

ACTIVE COMPARATOR

Participants who are Xpert-positive will be referred for TB treatment initiation while Xpert-negative participants will be followed up. Thus, the active case finding (ACF) standard of care package is POC Xpert.

Diagnostic Test: Xpert

Interventions

CAD DIAGNOSTIC_TEST

It is an artificial intelligence (AI) system for detection of TB on CXR images. The system input is a frontal CXR, and the outputs are 1) a heatmap indicating suspicious regions on the image; and 2) a score (0-100) which implies the likelihood that the x-ray image shows TB.

Also known as: CAD4TB and/or other AI/CAD software

CAD + POC Xpert

Xpert DIAGNOSTIC_TEST

A novel diagnostic for active case finding (GeneXpert MTB/RIF) for TB on sputum collected and performed at POC in a mobile van.

Also known as: GeneXpert System

CAD + POC Xpert; POC Xpert only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants willing to complete community-based symptom screening, finger-prick and venepuncture blood sampling, urine testing, and/or undergo TB and/or COVID-19 diagnostic testing.
• Provision of informed consent.
• Participant 18 years or above.
• HIV-positive or negative participants will be included.

You may not qualify if:

• Inability to provide informed consent (e.g., mentally impaired).
• Participants who have completed TB treatment in the last two months, or who have self-presented to their local TB clinic and are currently being worked up for suspected TB.
• Participants already diagnosed with active TB on treatment.
• Participants unable to commit to at least a two-month follow-up.
• Female participants who are pregnant or who refuse a urine pregnancy test.
• Participants in the community who cannot access healthcare due to severe ill health or lack of access to the local clinic.

Sponsors & Collaborators

• University of Cape Town: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• Zambart: collaborator
• Biomedical Research and Training Institute: collaborator
• Ospedale San Raffaele: collaborator
• Radboud University Medical Center: collaborator
• Foundation for Innovative New Diagnostics, Switzerland: collaborator
• University of Stellenbosch: collaborator

Study Sites (3)

University of Cape Town

Cape Town, Western Cape, South Africa

Location

Helen Ayles

Lusaka, Zambia

Location

Junior Mutsvangwa

Harare, Zimbabwe

Location

MeSH Terms

Conditions

Tuberculosis; COVID-19; HIV Infections

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Keertan Dheda, PhD

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 2, 2022
• Study Start: February 23, 2022
• Primary Completion: August 15, 2025
• Study Completion: December 1, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

ZA (1); ZI (1)