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

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ClinicalTrials.gov Identifier: NCT03168945
Recruitment Status : Recruiting
First Posted : May 30, 2017
Last Update Posted : May 30, 2017
Sponsor:
Collaborators:
Medical Research Council, South Africa
National Institutes of Health (NIH)
University of Cape Town Lung Institute
Information provided by (Responsible Party):
Keertan Dheda, University of Cape Town

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.


Condition or disease Intervention/treatment Phase
Tuberculosis Other: GeneXpert MTB/RIF Other: Smear microscopy Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Quantifying Infectiousness of Undiagnosed Tuberculosis Cases and the Impact of Enhanced Community-based Active Case Finding Strategy Using Novel Diagnostic Tools: A Randomized Controlled Trial
Study Start Date : November 2016
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Active Comparator: Novel diagnostics arm
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
Screening intervention: novel diagnostic for active case finding (GeneXpert MTB/RIF) for TB collected and performed at point-of-contact in a mobile van
Other Name: GeneXpert Omni

Placebo Comparator: Routine screening arm
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
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




Primary Outcome Measures :
  1. The time-to-treatment of culture-positive TB cases initiating TB treatment in each study arm. [ Time Frame: Within 2 months of enrollment, up to 24 months ]
    Time (in days) as determined by difference between enrolment date and date that treatment is commenced in local TB Clinic attendance register.


Secondary Outcome Measures :
  1. The proportion of culture-positive TB cases initiating TB treatment in each study arm. [ Time Frame: Within 2 months of enrolment, up to 26 months ]
    Proportion of culture-positive participants initiating treatment as determined by TC Clinic attendance register.

  2. The proportion of culture-positive TB cases completing 6-months of TB treatment in each study arm. [ Time Frame: Through study completion, up to 48 months ]
    Determined by confirming treatment completion (and discharge) by local TB Clinic.

  3. Accuracy of GeneXpert® Omni MTB/RIF at the point-of-care in a mobile unit. [ Time Frame: Through study completion, up to 48 months ]
    Accuracy of lab-based Xpert determined by inter-rater agreement with paired sample analysed using laboratory-based Xpert).

  4. Feasibility of performing GeneXpert® Omni MTB/RIF at the point-of-care in a mobile unit. [ Time Frame: Through study completion, up to 48 months ]
    Number of study days lost to operational problems with machine or van (recorded daily by study team in daily register). Furthermore, user adherence to test protocol, operator knowledge of the testing procedure, and confidence in the test and satisfaction with its ease of use will be tested by two standardised questionnaires employed and validated in our previous study on active case-finding using lab-based Xpert.

  5. User adherence to methodology of GeneXpert® Omni MTB/RIF at the point-of-care in a mobile unit. [ Time Frame: Through study completion, up to 48 months ]
    Confidence in the test and satisfaction with its ease of use will be tested by a standardised questionnaire employed and validated in our previous study on active case-finding using lab-based Xpert.

  6. User acceptance to methodology of GeneXpert® Omni MTB/RIF at the point-of-care in a mobile unit. [ Time Frame: Through study completion, up to 48 months ]
    Measured by standardised questionnaire assessing user adherence to test protocol, employed and validated in our previous study on active case-finding using lab-based Xpert.

  7. Cost per TB case detected between study arms. [ Time Frame: Through study completion, up to 48 months ]
    Cost-effectiveness analysis to be performed at study conclusion.

  8. Cost per TB case successfully completing treatment between study arms. [ Time Frame: Through study completion, up to 48 months ]
    Cost-effectiveness analysis to be performed at study conclusion.

  9. To contribute data and samples as part of the RePORT consortium in order to achieve a better understanding of the prognosis of TB disease and the pathogenesis of progression from TB exposure to disease. [ Time Frame: Through study completion, up to 48 months ]
    Sputum, Blood, Urine and saliva samples will be collected and biobanked for future analyses.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria for TB suspects

  1. 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.
  2. Provision of informed consent.
  3. 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.
  4. 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
  5. Any HIV+ve adult (older than 18 years).
  6. 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.

Confirmatory Inclusion criteria for RePORT sample collection

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.

iii. Mtb identified from either liquid or solid culture is acceptable, and may be from either clinical or study-related specimens.

iv. Those who have extra-pulmonary manifestations of TB in addition to pulmonary TB may also be enrolled.

Participants who fail to meet the confirmatory inclusion criteria noted above will be discontinued from the RePORT aspect of the study. However, specimens that were previously collected from the participant may be retained for use as control specimens, and the participants may still continue participation in the XACT-2 study.

Exclusion criteria for TB suspects

  1. Inability to provide informed consent (e.g. mentally impaired).
  2. Patients self-presenting to the TB clinics.
  3. 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).

  4. 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).
  5. 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.
  6. Is currently imprisoned.

Inclusion criteria for Household contacts (HHC)

  1. Adult (> 18 years old) with significant recent exposure (within the past 6 months) to an adult with untreated or inadequately treated pulmonary TB.
  2. 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.
  3. 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.
  4. 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.)

Exclusion Criteria for Household contacts

  1. 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).
  2. 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.
  3. Is currently imprisoned.

Exclusion from the RePORT aspect of the study (patients may still be included in the XACT II study)

  1. Participants enrolled as active TB cases will be discontinued from the study for the following reasons:

    a. More than 1 week of anti-TB therapy was received before the following minimum required baseline laboratory specimens were collected: i. Sputum for culture and Mtb isolate; ii. Sputum for storage; iii. Blood and plasma; and iv. Urine b. The provisional pulmonary TB diagnosis is not confirmed as defined by the protocol (see Confirmatory Inclusion Criteria listed above); c. An HIV test was not completed within the Month 1 Visit window; d. A study outcome occurred: i. Treatment failure (bacteriologic or clinical); ii. TB relapse (bacteriologic or clinical); iii. Emerging resistance; or iv. Completion of the 6-Month Post-Treatment Visit.

  2. Household contacts will be discontinued from the study for the following reasons:

    a. A study outcome occurred: i. Active TB develops before the Month 24 Visit; the participant may enroll as an active TB participant if all eligibility criteria are met; or ii. Completion of the Month 24 Visit.

  3. Participants will be discontinued from the study for any of the following reasons:

    1. The participant/parent/legal guardian withdraws consent and/or assent;
    2. The participant is lost to follow-up or moves out of the area;
    3. The participant dies;
    4. The participant was inadvertently enrolled;
    5. The investigator determines that further participation would be detrimental to the health or well-being of the participant;
    6. The study is stopped by a funding organization or other government agency; or
  4. The study has to stop for other administrative reasons.

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): NCT03168945


Contacts
Contact: Aliasgar Esmail, MBChB 021 406 6119 ext 6119 a.esmail@uct.ac.za
Contact: Suzette Oelofse, MBChB 021 406 6119 ext 6119 suzette.oelofse@uct.ac.za

Locations
South Africa
University of Cape Town Recruiting
Cape Town, Western Province, South Africa, 7945
Contact: Keertan Dheda, MBChB, PhD    +27214067650 ext 7650    keertan.dheda@uct.ac.za   
Contact: Aliasgar Esmail, MBChB    +27214066119 ext 6119    a.esmail@uct.ac.za   
Principal Investigator: Keertan Dheda, MBChB, PhD         
Sub-Investigator: Greg Calligaro, MBChB         
Sub-Investigator: Aliasgar Esmail, MBChB         
Sub-Investigator: Oelofse Suzette, MBChB         
Sub-Investigator: Randall Philippa, PhD         
Sub-Investigator: Pooran Anil, PhD         
Sponsors and Collaborators
University of Cape Town
Medical Research Council, South Africa
National Institutes of Health (NIH)
University of Cape Town Lung Institute
Investigators
Principal Investigator: Keertan Dheda, MBChB, PhD Head of Lung Infection and Immunity Unit and Division and Pulmonology

Publications of Results:
Responsible Party: Keertan Dheda, Principal Investigator, University of Cape Town
ClinicalTrials.gov Identifier: NCT03168945     History of Changes
Other Study ID Numbers: XACT-2
OISE-16-62105-1 ( Other Grant/Funding Number: U.S. Civilian Research and Development Foundation )
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: May 30, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Keertan Dheda, University of Cape Town:
Active Case Finding

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections