Xpert Active Case-finding Trial 2: Community-based Active Case-finding for Tuberculosis in South Africa

NCT03168945 | Completed

• 2 other identifiers: XACT-2OISE-16-62105-1
• Study Type: interventional
• Target: 608
• Locations: 1 country
• Sites: 1

Brief Summary

TB kills most people with HIV in Africa. TB is out of control. Radically different approaches to deal with the disease is therefor needed. It is known that intensified case finding works in high HIV prevalence environments. However, the poor performance of conventional diagnostics makes the strategy costly and unpalatable for policy makers. If it can be shown that a package of new diagnostic technologies significantly enhances ease and speed of diagnosis, and time to treatment initiation when using intensified case finding, this will usher the way for further studies and policy adjustments to tackle TB. Thus, the work, if found to be useful, could have major policy implications The purpose of this study will be to determine the diagnostic yield, impact and feasibility of community-based intensified TB case finding using symptom screening, point-of-care TB testing (Xpert Omni), point-of-care HIV testing and CD4 count (Alere PIMA), if HIV-infected, together with a clinic-based diagnostic package (sputum smear microscopy, MGIT sputum culture, and digital chest radiograph). Additionally, the study will assess the infectiousness of previously undiagnosed TB cases in the community using cough aerosol sampling technology (CASS) and will determine the genomic, transcriptomic and lipidomic profile of TB isolates from patients undergoing CASS sampling. The cost-effectiveness of using a novel TB diagnostic platform (Xpert Omni) for intensified case finding compared to conventional methods will also be evaluated. \~6000 people will be screened to enrol 600 participants with suspected TB. It is expected that using the GeneXpert® Omni POC mobile clinic of 2- to 3-person team of healthcare workers in an inexpensive panel van will substantially reduce the time to treatment initiation, and the proportion of individuals initiating and completing TB treatment. Investigators will also review and follow up Household contacts of active TB participants. As part of the study investigators will also contribute data and specimens to the RePORT consortium (Regional Prospective Observational Research for Tuberculosis), that aims to create a multinational bank with the primary objective of providing specimens and data to RePORT consortia biomarker researchers and their collaborators over the next decade to achieve a better understanding of the prognosis of TB disease; and the pathogenesis of progression from TB exposure to disease.

Conditions

Tuberculosis

Keywords

Active Case Finding

Outcome Measures

Primary Outcomes (1)

• The time-to-treatment of culture-positive TB cases initiating TB treatment in each study arm.

  Time (in days) as determined by difference between enrolment date and date that treatment is commenced in local TB Clinic attendance register.

  Within 2 months of enrollment, up to 24 months

Secondary Outcomes (9)

• The proportion of culture-positive TB cases initiating TB treatment in each study arm.

  Within 2 months of enrolment, up to 26 months

• The proportion of culture-positive TB cases completing 6-months of TB treatment in each study arm.

  Through study completion, up to 48 months

• Accuracy of GeneXpert® Omni MTB/RIF at the point-of-care in a mobile unit.

  Through study completion, up to 48 months

• Feasibility of performing GeneXpert® Omni MTB/RIF at the point-of-care in a mobile unit.

  Through study completion, up to 48 months

• User adherence to methodology of GeneXpert® Omni MTB/RIF at the point-of-care in a mobile unit.

  Through study completion, up to 48 months

Study Arms (2)

Novel diagnostics arm

ACTIVE COMPARATOR

The intervention is to screen a sputum specimen collected on a participant with suspected TB in the community at the point-of-contact in a mobile van using an on-site GeneXpert MTB/RIF machine

Other: GeneXpert MTB/RIF

Routine screening arm

PLACEBO COMPARATOR

The control arm is to send a sputum specimen collected on a participant with suspected TB at the mobile van for routine smear microscopy at a laboratory

Other: Smear microscopy

Interventions

GeneXpert MTB/RIF OTHER

Screening intervention: novel diagnostic for active case finding (GeneXpert MTB/RIF) for TB collected and performed at point-of-contact in a mobile van

Also known as: GeneXpert Omni

Novel diagnostics arm

Smear microscopy OTHER

Screening intervention: routine diagnostic test (smear microscopy) for active case finding for TB on sputum collected at point-of-contact in a mobile van but sent to laboratory

Routine screening arm

Eligibility Criteria

• Age: 18 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, urine testing, blood testing for HIV and/or undergo TB diagnostic tests at the local TB clinic.
• 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, 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.)
• To be eligible for the RePORT sample collection aspect of the study, the participant must have either CXR findings consistent with TB, and/or are sputum smear positive by microscopy or by rapid diagnostic test, such as GeneXpert.
• a.) Adults must have pulmonary disease confirmed by culture. i. Mtb identified by culture of expectorated or induced sputum. ii. Mtb identified by culture results from respiratory secretions obtained by broncho-alveolar lavage or bronchial wash may not be used to determine study eligibility.

You may not qualify if:

• Inability to provide informed consent (e.g. mentally impaired).
• Patients self-presenting to the TB clinics.
• Patients who have completed TB treatment in the last 2 months or received \>1 week (daily or intermittent doses) of any drugs with anti-TB activity within 30 days prior to provisional enrolment, including:
• Any drug or combination of drugs typically used in a multidrug anti-TB therapy (isoniazid \[INH\], rifampicin, pyrazinamide, ethambutol); Any fluoroquinolone (e.g., ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, sparfloxacin, and gatifloxacin); Any other drugs with anti-TB activity (e.g., clofazamine, aminoglycosides \[amikacin, kanamycin\], or capreomycin).
• Plans to move from his/her current residence, which would interfere with the participant's ability to complete all study visits (through the 6-Month Post-Treatment Visit).
• 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.
• Is currently imprisoned.
• 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-pulmonary TB. If clinical signs or symptoms of TB are present, CXR 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 24 Visit).
• 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.
• Is currently imprisoned.
• Participants enrolled as active TB cases will be discontinued from the study for the following reasons:

Sponsors & Collaborators

• University of Cape Town: lead
• Medical Research Council, South Africa: collaborator
• National Institutes of Health (NIH): collaborator
• University of Cape Town Lung Institute: collaborator

Study Sites (1)

University of Cape Town

Cape Town, Western Province, 7945, South Africa

Location

Related Publications (2)

• Calligaro GL, Zijenah LS, Peter JG, Theron G, Buser V, McNerney R, Bara W, Bandason T, Govender U, Tomasicchio M, Smith L, Mayosi BM, Dheda K. Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicentre randomised controlled trial. Lancet Infect Dis. 2017 Apr;17(4):441-450. doi: 10.1016/S1473-3099(16)30384-X. Epub 2017 Jan 5.

  PMID: 28063795 RESULT

• Esmail A, Randall P, Oelofse S, Tomasicchio M, Pooran A, Meldau R, Makambwa E, Mottay L, Jaumdally S, Calligaro G, Meier S, de Kock M, Gumbo T, Warren RM, Dheda K. Comparison of two diagnostic intervention packages for community-based active case finding for tuberculosis: an open-label randomized controlled trial. Nat Med. 2023 Apr;29(4):1009-1016. doi: 10.1038/s41591-023-02247-1. Epub 2023 Mar 9.

  PMID: 36894651 DERIVED

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

  Head of Lung Infection and Immunity Unit and Division and 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

Study Record Dates

• First Submitted: December 23, 2016
• First Posted: May 30, 2017
• Study Start: November 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: August 1, 2020
• Last Updated: March 30, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)