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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

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ClinicalTrials.gov Identifier: NCT05220163
Recruitment Status : Recruiting
First Posted : February 2, 2022
Last Update Posted : April 5, 2022
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Zambart
Biomedical Research and Training Institute
Ospedale San Raffaele
Radboud University Medical Center
Foundation for Innovative New Diagnostics, Switzerland
University of Stellenbosch
Information provided by (Responsible Party):
Keertan Dheda, University of Cape Town

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.

Condition or disease Intervention/treatment Phase
Tuberculosis COVID-19 HIV Infections Diagnostic Test: CAD Diagnostic Test: Xpert Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: 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
Actual Study Start Date : February 23, 2022
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

Drug Information available for: X-Rays

Arm Intervention/treatment
Experimental: CAD + POC Xpert
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
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.
Other Name: CAD4TB and/or other AI/CAD software

Diagnostic Test: Xpert
A novel diagnostic for active case finding (GeneXpert MTB/RIF) for TB on sputum collected and performed at POC in a mobile van.
Other Name: GeneXpert System

Active Comparator: POC Xpert only
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
A novel diagnostic for active case finding (GeneXpert MTB/RIF) for TB on sputum collected and performed at POC in a mobile van.
Other Name: GeneXpert System




Primary Outcome Measures :
  1. Time to detection of microbiologically proven TB [ Time Frame: Through study completion, up to 48 months ]
    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.


Secondary Outcome Measures :
  1. Feasibility of CAD + POC Xpert performed by minimally trained healthcare workers [ Time Frame: Through study completion, up to 48 months ]
  2. Number of infectious TB cases detected (defined by cough aerosol sampling system [CASS] and/or smear and/or cavitatory disease positive) [ Time Frame: Through study completion, up to 48 months ]
  3. 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) [ Time Frame: Through study completion, up to 48 months ]
  4. Time to TB treatment initiation (both the median time to treatment in each group and time to event [treatment] analyses will be conducted) [ Time Frame: Through study completion, up to 48 months ]
  5. Yield of culture positive TB in household contacts of index participants [ Time Frame: Through study completion, up to 48 months ]
  6. NPV and false negative rate (TB cases missed per 1 000 persons screened) of CAD and other screening tests for TB [ Time Frame: Through study completion, up to 48 months ]
  7. Reduction in number of sputum induction procedures and/or Xpert tests performed [ Time Frame: Through study completion, up to 48 months ]
  8. Global and country-specific cost-effectiveness analysis for each strategy [ Time Frame: Through study completion, up to 48 months ]
  9. Transmission and disease burden impact using modelling based on exposure scores, imaging, and CASS [ Time Frame: Through study completion, up to 48 months ]
  10. Rates or prevalence of microbiological versus probable (clinical TB) [ Time Frame: Through study completion, up to 48 months ]
  11. Proportion of culture-positive TB cases completing three- and six-months of TB treatment in each study arm [ Time Frame: Through study completion, up to 48 months ]
  12. Middleware/dashboard design requirements and deployment models for each strategy [ Time Frame: Through study completion, up to 48 months ]
  13. Feasibility and yield of POC Xpert (Xpress cartridge) for COVID-19 detection [ Time Frame: Through study completion, up to 48 months ]
  14. Feasibility and performance of CAD4COVID for PCR-positive COVID-19 detection [ Time Frame: Through study completion, up to 48 months ]
  15. Feasibility of a novel mass screening strategy for COVID-19 that uses pooling of specimen from a group of COVID-19 suspects [ Time Frame: Through study completion, up to 48 months ]

Other Outcome Measures:
  1. 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) [ Time Frame: Through study completion, up to 48 months ]
  2. Economic outcome: Direct comparison of the cost effectiveness of ACF compared to passive case finding (the current public health practice) [ Time Frame: Through study completion, up to 48 months ]
  3. Economic outcome: Cost effectiveness considering drug resistant TB (DR-TB) and HIV prevention [ Time Frame: Through study completion, up to 48 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

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): NCT05220163


Contacts
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Contact: Alex J Scott, MBChB 00274066669 alex.scott@uct.ac.za
Contact: Aliasgar Esmail, MD 00274066119 a.esmail@uct.ac.za

Locations
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South Africa
University of Cape Town Recruiting
Cape Town, Western Cape, South Africa
Contact: Keertan Dheda, MD/PhD       keertan.dheda@uct.ac.za   
Contact: Ali Esmail, MD       a.esmail@uct.ac.za   
Zambia
Helen Ayles Not yet recruiting
Lusaka, Zambia
Contact: Helen Ayles, MBChB         
Zimbabwe
Junior Mutsvangwa Not yet recruiting
Harare, Zimbabwe
Contact: Junior Mutsvangwa, MBChB         
Sponsors and Collaborators
University of Cape Town
European and Developing Countries Clinical Trials Partnership (EDCTP)
Zambart
Biomedical Research and Training Institute
Ospedale San Raffaele
Radboud University Medical Center
Foundation for Innovative New Diagnostics, Switzerland
University of Stellenbosch
Investigators
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Principal Investigator: Keertan Dheda, PhD University of Cape Town
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Responsible Party: Keertan Dheda, Professor, University of Cape Town
ClinicalTrials.gov Identifier: NCT05220163    
Other Study ID Numbers: XACT-19
First Posted: February 2, 2022    Key Record Dates
Last Update Posted: April 5, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Keertan Dheda, University of Cape Town:
Tuberculosis
Active case finding
Computer assisted diagnosis
Screening
COVID-19
Additional relevant MeSH terms:
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COVID-19
Tuberculosis
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses