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

NCT04303104 | Active Not Recruiting DMC

• 1 other identifier: XACT-3
• Study Type: interventional
• Target: 3,394
• Locations: 3 countries
• Sites: 3

Brief 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

Keywords

TB Screening; Active Case Finding; Mobile versus Centralized

Outcome Measures

Primary Outcomes (1)

• Proportion with PTLF (defined as test positive patients failing to initiate treatment by 60 days) and/ or the proportion of infectious TB patients (smear positive and/ or with cavitatory disease) not initiating treatment within 14 days of diagnosis.

  The proposed primary outcome measure is a surrogate of transmission and disease amplification (especially of the 'missed' highly infectious cases). Thus, the composite outcome serves as a surrogate of those who will experience a poor outcome (the missing cases) and disease amplification (transmission of TB).

  Within 2 months of enrollment, up to 24 months

Secondary Outcomes (10)

• Proportion of culture-positive patients failing to initiate treatment in each study arm within 14 days of diagnosis.

  Within 2 months of enrolment, up to 26 months

• Time to TB treatment initiation

  Within 2 months of enrollment, up to 24 months

• Time-specific proportion of patients initiated on TB treatment up to 60 days.

  Within 2 months of enrolment, up to 26 months

• Feasibility of Xpert being performed by minimally trained health care workers at point-of-care using.

  Through study completion, up to 48 months

• Cost effectiveness analysis in each of the four countries.

  Through study completion, up to 48 months

Study Arms (2)

Mobile ACF

ACTIVE COMPARATOR

Xpert Edge performed at point-of-care employing a low-cost panel van that is staffed by three health care workers. Patients identified with active TB will be initiated on TB treatment on the same day at the nearest clinic. On site HIV testing will also be offered. Thus, the interventional package is one of ACF + POC TB testing (TB testing by Xpert will occur on site at the van).

Other: GeneXpert Edge

Centralised ACF

PLACEBO COMPARATOR

Similar to active arm but Xpert Ultra will be performed at a centralized laboratory (samples will be transported to the laboratory with results being available in a few days). Thus, the standard of care package is ACF + distant TB testing (TB testing by Xpert will occur at a distant laboratory site).

Other: GeneXpert Ultra

Interventions

GeneXpert Edge OTHER

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

Mobile ACF

GeneXpert Ultra OTHER

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

Centralised ACF

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Community participant willing to complete community-based symptom screening, finger-prick blood testing, and/or undergo TB diagnostic testing.
• Provision of informed consent.
• Has documentation of, or willingness to be tested for HIV infection. HIV testing does not need to be repeated if there is written documentation of a confirmed positive test at any time in the past.
• HIV-negative adults (older than 18 years) with 1 or more of the following:• cough ≥ 2 weeks• loss of weight• Fever• night sweats• generalized fatigue• haemoptysis• chest pain.
• Any HIV+ve adult (older than 18 years).
• Agrees to the collection and storage of blood, urine, sputum specimens for use for future research. (The participant may decline collection of specimens for human genetic research and still be eligible for the study).

You may not qualify if:

• Inability to provide informed consent (e.g. mentally impaired).
• Patients who have completed TB treatment in the last 2 months, or who have self-presented to their local TB clinic and are currently being worked up for suspected TB.
• Patients already diagnosed with active TB.
• Patients unable to commit to a two month follow up or who do not wish to be followed up.
• Adult (\> 18 years old) with significant recent exposure (within the past 6 months) to an adult with untreated or inadequately treated pulmonary TB.
• No clinical signs or symptoms of active TB that include, but are not limited to: persistent cough, haemoptysis, fever, unintended weight loss or failure to thrive (children), fatigue or lethargy, night sweats, pleuritic chest pain, draining lymph node, or other evidence of extra-pulmonaryTB. If clinical signs or symptoms of TB are present, Chest X-Ray and/or sputum culture results must be included in the overall evaluation to rule out active TB.
• Has signed a written consent or witnessed oral consent in the case of illiteracy, prior to his/her first sample or other study-specific data being collected.
• Agrees to the collection and storage of blood, urine, saliva and sputum specimens for use for future research. (The participant may decline collection of specimens for human genetic research and still be eligible for the study.)
• Plans to move from his/her current residence, which would interfere with the participant's ability to complete all study visits (through the Month 24Visit).
• Has an active psychiatric condition, or alcohol or drug dependence that, in the opinion of the site investigator or designee, might interfere with the ability to give true informed consent and to adhere to the study requirements.

Sponsors & Collaborators

• University of Cape Town: lead
• Zambart (University of Zambia), Zambia: collaborator
• Instituto Nacional de Saúde, Mozambique: collaborator
• Biomedical Research and Training Institute, Zimbabwe: collaborator
• Radboud University Medical Center: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• University of Cape Town Lung Institute: collaborator

Study Sites (4)

Bindiya Meggi

Maputo, Mozambique

Location

University of Cape Town

Cape Town, Western Cape, 7925, South Africa

Location

Helen Ayles

Lusaka, Zambia

Location

Junior Mutsvangwa

Harare, Zimbabwe

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Keertan Dheda, MBChB, PhD

  Lung Infection and Immunity Unit and Division of Pulmonology

  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: Principal Investigator

Model Details: Xpert-oriented active case-fining model for TB: portable GXPU/molecular device hosted in a mobile mini-clinic to perform ACF in peri-urban informal settlements. Open-label randomisation to GXPU performed at POC or a central laboratory.

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 10, 2020
• Study Start: March 26, 2021
• Primary Completion: August 30, 2024
• Study Completion: December 30, 2025
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

ZA (1); MO (1); ZI (1)