Clinical trial NCT05941052: Assessing Diagnostics At Point-of-care for Tuberculosis
Official title: Supporting, Mobilizing and Accelerating Research for Tuberculosis Elimination (SMART4TB)- Technical Area (TA) 1: Diagnostics- Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tuberculosis
Keywords: Tuberculosis
Diagnostics
Global Health
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University Hospital Heidelberg
name: KNCV Tuberculosis Foundation
name: Bingham University
name: University of California, Irvine
name: De La Salle University Medical Center
name: Centre for Infectious Disease Research in Zambia
name: Johns Hopkins University
First posted: 2023-07-12
Enrollment: 1350
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Every year, more than 3 million people with TB remain undiagnosed and 1 million die. Better diagnostics are essential to reducing the enormous burden of TB worldwide. The Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) study seeks to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests.

Detailed description: The Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) seeks to identify and rigorously assess promising, design-locked point-of-care (POC) tuberculosis (TB) diagnostic tests (hereafter referred to as "novel tests") in clinical studies conducted in settings of intended use. Rapid diagnosis and effective treatment are critical for improving patient outcomes and reducing TB transmission. However, nearly one-third of people with TB are not diagnosed or reported to public health authorities.The different types of tests required to reduce this "diagnostic gap" have been described in the form of target product profiles (TPPs) defined by the World Health Organization (WHO). The highest priority TPP is that for a point-of-care, non-sputum biomarker-based test to facilitate rapid TB diagnosis using easily accessible samples (i.e., a biomarker-based diagnostic test). The ADAPT study will evaluate the sensitivity, specificity and yield of novel diagnostic tests against a reference standard including sputum Xpert® Mycobacterium tuberculosis/Rifampicin (MTB/RIF) Ultra and sputum mycobacterial culture among adolescents and adults with presumptive TB (based on having TB symptoms, or TB risk factor + positive TB screening test) presenting to outpatient health facilities in high burden countries. In addition, the usability and acceptability of novel TB diagnostic tests will be assessed through direct observations and surveys of routine health workers.

Eligibility criteria: Novel TB triage and diagnostic tests:

Inclusion Criteria-

The investigators will include non-hospitalized adults (age ≥ 12 years) with either:

1. cough ≥2 weeks' duration, a commonly accepted criterion for identifying people with presumed pulmonary TB (to facilitate standardization across sites and comparison of test performance across sub-groups; OR
2. risk factors for which TB screening is recommended (HIV infection, self-reported close contact, history of mining work). People with risk factors will be included if they screen positive for TB based on WHO-recommended screening tools as specified below:

Positive TB screening definitions by risk factor:

1. People Living with Human Immunodeficiency Virus (PLHIV) (Risk Factor): C Reactive Protein (CRP) \>5 mg/dL OR abnormal chest x-ray (CXR)
2. Self-reported Close Contact (Risk Factor): abnormal CXR History of mining work (Risk Factor): abnormal CXR

Exclusion Criteria-

1. Completed latent or active TB treatment within the past 12 months (to increase TB prevalence and reduce false-positive results, respectively);
2. Have taken any medication with anti-mycobacterial activity (including fluoroquinolones) for any reason, within 2 weeks of study entry (to reduce false-negatives);
3. Reside \>20km from the study site or are unwilling to return for follow-up visits; OR
4. Are unwilling to provide informed consent

Assessment of the usability of novel TB tests:

Inclusion Criteria-

The investigators will include health workers at each clinical site who are:

1. aged ≥18 years; AND
2. involved in routine TB testing (collecting specimens for or performing TB tests).

Exclusion Criteria-

The investigators will exclude staff who are:

1) unwilling to provide informed consent

Primary outcomes:
measure: Proportion with positive index test result among participants with tuberculosis (TB)
timeFrame: 2 years
measure: Proportion with negative index test result among participants without tuberculosis (TB)
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Abuja
country: Nigeria
facility: Zankli Research Center, Bingham University
city: Dasmariñas
country: Philippines
facility: De La Salle Medical and Health Sciences Institute
city: Lusaka
country: Zambia
facility: Centre for Infectious Disease Research in Zambia
Study officials:
affiliation: University of California, Irvine
name: Adithya Cattamanchi
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cho SN, Brennan PJ. Tuberculosis: diagnostics. Tuberculosis (Edinb). 2007 Aug;87 Suppl 1:S14-7. doi: 10.1016/j.tube.2007.05.001. Epub 2007 Jun 20.
citation: World Health Organization. Global tuberculosis report Geneva, Switzerland: World Health Organization, 2015.
citation: Organization WH. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva, Switzerland: WHO Press, 2014.
citation: Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O'Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010 Sep 9;363(11):1005-15. doi: 10.1056/NEJMoa0907847. Epub 2010 Sep 1.
citation: Walusimbi S, Bwanga F, De Costa A, Haile M, Joloba M, Hoffner S. Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis. BMC Infect Dis. 2013 Oct 30;13:507. doi: 10.1186/1471-2334-13-507.
citation: Xpert MTB/RIF Implementation Manual: Technical and Operational 'How-To'; Practical Considerations. Geneva: World Health Organization; 2014. Available from http://www.ncbi.nlm.nih.gov/books/NBK254323/
citation: Subbaraman R, Nathavitharana RR, Satyanarayana S, Pai M, Thomas BE, Chadha VK, Rade K, Swaminathan S, Mayer KH. The Tuberculosis Cascade of Care in India's Public Sector: A Systematic Review and Meta-analysis. PLoS Med. 2016 Oct 25;13(10):e1002149. doi: 10.1371/journal.pmed.1002149. eCollection 2016 Oct.