Prospective Evaluation of Novel Diagnostics for Tuberculosis in KwaZulu-Natal, South Africa

Tuberculosis (TB) infects nearly two billion people and has become the leading infectious cause of mortality worldwide, due in part to inadequate diagnostic and prognostic tests. Older diagnostic tools, such as acid-fast staining, and newer diagnostic tests, such as nucleic acid amplification, are either insensitive, expensive, or not suitable for use at the clinical point-of-care. Therefore, novel diagnostic tests are needed to diagnose active TB disease among adults, people living with HIV (PLHIV), and children in TB-endemic countries. In this project, the investigators will conduct clinical evaluation studies of emerging TB diagnostic tests among (1) hospitalized adults, (2) ambulatory adults in outpatient clinics, and (3) children <12 years suspected of having active TB disease. the investigators will also maintain a biorepository of well-characterized clinical specimens that can be used for either retrospective validation of TB diagnostic tests, establishing a reference LAM test, or to share with partners developing novel TB diagnostics, including new LAM antibodies. The project will be coordinated at the University of Washington, and conducted in partnership with clinical research partners in South Africa, including Umkhuseli Innovation and Research Management (UIRM) and the National Health Laboratory Service (NHLS). The project team is well-equipped to serve as a central clinical research site to evaluate new and emerging point-of-care TB diagnostics, particularly novel urinary LAM assays, at the on-site TB Diagnostics Research Laboratory at Edendale Hospital in KwaZulu-Natal, South Africa.

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Key information

Conditions

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

Age range

12 month and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Edendale Hospital

Pietermaritzburg, 3201, South Africa

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Phase I

Eligibility for hospitalized and ambulatory adults:

≥16 years old
Positive Xpert MTB/RIF Ultra test (TB-positive cohort) or no suspicion of clinical TB (TB-negative cohort)
Have a documented HIV test result or agrees to test for HIV
Have NOT received IPT within prior 3 months
Have NOT received anti-TB treatment for more than 24 hours
Willing/able to provide written informed consent

Phase II:

Eligibility for hospitalized adults:

≥16 years old
Admitted to inpatient medical ward <72 hours
Have a documented positive HIV test
Have NOT received IPT within prior 3 months
Have NOT received anti-TB treatment for more than 24 hours
Willing/able to provide written informed consent

Study population description:

Eligibility for Xpert+ adults (hospitalized and attending outpatient clinics)

≥16 years old
Have a documented HIV test result or agrees to test for HIV
Positive Xpert MDR/RIF Ultra test documented.
Have NOT received anti-TB treatment for more than 24 hours
Willing/able to provide written informed consent

Eligibility for children
children <12 years of age
suspected of having active TB disease by clinical team
Have a documented HIV test result or agrees to test for HIV
Have not had IPT within 3 months
Have not received anti-TB treatment for more than 24 hours within the prior 5 days
Parent or guardian is willing/able to provide written informed consent

Treatment and study plan

Primary outcomes

Number of Participants Classified with TB Case Definition

Time frame: Baseline

TB positive: A person with a positive Xpert MTB/RIF test or TB culture on any bodily fluid specimen that was obtained/tested within 5 days of enrollment.

Probable TB: A person with compatible symptoms, signs, histopathological specimens and imaging for TB, but without a positive TB culture or Xpert test on any specimen; empirically initiated on TB treatment.

TB negative: A person with a primary hospital diagnosis other than TB, who has no clinical suspicion for TB, and no diagnostic TB testing ordered by the treating team.

TB negative (TB excluded): A person with all reference microbiological testing for TB returning negative, including negative Xpert, negative TB culture, other investigations for TB negative (e.g. histopathology, imaging) and either clinical improvement in the absence of anti-TB therapy or alternate diagnosis determined. In addition, no incident TB diagnosis made (including empiric anti-TB treatment initiation) within the 2 months following enrollment.

Secondary outcomes

Number of Participants with TB Treatment Outcome

Time frame: 2 Month, 6 Month
- Confirmed TB: Bacteriological confirmation obtained: culture or Xpert MTB/RIF from at least one specimen.
- Probable TB: Bacteriological confirmation not obtained AND at least 2 of the following:
- Symptoms/signs suggestive of TB (as defined)
- Chest radiograph or abdominal ultrasound consistent with TB
- Close TB exposure or immunologic evidence of M. tuberculosis infection
- Positive response to anti-TB treatment (requires documented positive clinical response on TB treatment)
- TB negative/unlikely: Bacteriological confirmation NOT obtained AND criteria for "unconfirmed tuberculosis" NOT met.

Sponsors and collaborators

Lead sponsor

University of Washington

Other

Collaborators

KwaZulu Natal Department of Health
PATH
Salus Ltd.
Umkhuseli Innovation and Research Management (UIRM)
University of KwaZulu

Registry information

Acronym: PROVE-TB

Important dates

Study start: 2019
Primary completion: 2022
Study completion: 2022
First posted: Oct 12, 2020
Registry last updated: Aug 7, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed