Xpert Active Case-finding Trial 3 (XACT-3)

Summary

TB remains the foremost infectious disease killer globally. A startling statistic is that two out of every five TB cases globally (40%) remain undiagnosed and untreated. These 'missed' or undiagnosed cases are disproportionately concentrated in large peri-urban 'slums' and informal settlements of large cities in Africa and Asia (they are frequently minimally symptomatic but remain infectious).

The lack of a sensitive low cost same-day test represented a major challenge to active community-based case finding (ACF) compared to the current model where patients 'self-seek' care (passive case finding). More recently, sensitive TB DNA-detection tests called Gene Xpert (Xpert) have become available. This is a nucleic acid amplification test-based technology which can rule-in a diagnosis of TB in two thirds of smear negative pulmonary TB cases. GeneXpert® has now been rolled out in many African countries and is the frontline TB test in primary care clinics in South Africa. The investigators recently showed that GeneXpert® significantly reduced the time to treatment initiation in the setting of passive case finding (elaborated in next section). The investigators further showed that GeneXpert® can be performed by a minimally trained healthcare worker. However, historically technical and logistical demands meant that the GeneXpert® MTB-RIF assay was not ideally suited to use at point of care and in South Africa it is still centrally located.

Small portable battery-operated versions of these tests are now available (EDGE, GeneXpert two-module mobile platform). The investigators conducted a large study in South Africa and Zimbabwe (published in 2016) that showed that using the old non-portable version of Xpert on a mini-truck equipped with a generator was feasible and highly effective for ACF. A subsequent study funded by the American government (XACT II), showed that using the portable version of Xpert on the back of a small low-cost scalable panel van (in effect a mobile mini-clinic) was feasible and had a very high pick-up rate of TB in peri-urban communities (\~10% of those undergoing targeted screening). In this study, the investigators will test the hypothesis that community-based active case finding (ACF) using Gene Xpert Edge (in a low cost scalable mini-mobile clinic) performed at point-of-care (POC) is feasible and more effective (lower proportion of TB cases failing to initiate treatment especially if they are 'super-spreaders' i.e. highly infectious) than Xpert performed in a centralised laboratory.

Conditions

• Tuberculosis

Interventions

OTHER

GeneXpert Edge

Screening intervention: novel diagnostic for Active Case Finding (GeneXpert MTB/RIF) for TB on sputum collected and performed at point-of-contact in a mobile van

OTHER

GeneXpert Ultra

Screening intervention: novel diagnostic test for Active Case Finding (GeneXpert MTB/RIF) for TB on sputum collected at point-of-contact in a mobile van but sent to laboratory

Sponsors & Collaborators

• University of Zambia

  collaborator OTHER

• Instituto Nacional de Saúde, Mozambique

  collaborator OTHER_GOV

• Biomedical Research and Training Institute, Zimbabwe

  collaborator OTHER

• Radboud University Medical Center

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  collaborator OTHER

• University of Cape Town Lung Institute

  collaborator OTHER

• University of Cape Town

  lead OTHER

Principal Investigators

• Keertan Dheda, MBChB, PhD · Lung Infection and Immunity Unit and Division of Pulmonology

Study Design

Allocation

RANDOMIZED

Purpose

SCREENING

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-03-26

Primary Completion

2025-06-30

Completion

2025-12-30

Countries

• Mozambique
• South Africa
• Zambia
• Zimbabwe

Study Locations