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)

Overview

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.

Interventions

• Diagnostic test Tongue swab-based molecular assays
  The investigators will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.

Primary outcome measures

• Proportion with positive index test result among participants with tuberculosis (TB) [Time frame: 2 years]
• Proportion with negative index test result among participants without tuberculosis (TB) [Time frame: 2 years]

Eligibility criteria

Novel TB triage and diagnostic tests:

Inclusion Criteria-

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

• 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
• 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:

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

Exclusion Criteria-

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

• aged ≥18 years; AND
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Nigeria · 1 center

• Zankli Research Center, Bingham University — Abuja

Philippines · 1 center

• De La Salle Medical and Health Sciences Institute — Dasmariñas

Zambia · 1 center

• Centre for Infectious Disease Research in Zambia — Lusaka

Publications

• 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. PMID 17584529
• World Health Organization. Global tuberculosis report Geneva, Switzerland: World Health Organization, 2015.
• Organization WH. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva, Switzerland: WHO Press, 2014.
• 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. PMID 20825313
• 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. PMID 24172543
• 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/ PMID 25473699
• 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. PMID 27780217
• Yerlikaya S, Chirwa M, Ajide B, Castro MDM, Ha H, Kato-Maeda M, Kisakye E, Marcelo D, Mochizuki T, Rockman L, Steadman A, Thangakunam B, Bimba JS, Christopher DJ, Muyoyeta M, Phan H, Theron G, Yu C, Kremer K, Phillips PPJ, Nahid P, Denkinger CM, Cattamanchi A, Andama A; R2D2 TB Network and SMART4TB Consortia. Pulmonary Tuberculosis Detection with MiniDock MTB Using Swab Samples. N Engl J Med. 2026 PMID 42054680

Identifiers

NCT: NCT05941052 · 7200AA22RFA00004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗