Start4All - Start Taking Action for TB Diagnosis (DARE-TB)

Официальное название

Start 4 All - DARE-TB

Обзор

DARE-TB has been designed to address critical evidence gaps on the diagnostic performance and operational value of near point-of-care (NPOC) nucleic acid amplification tests (NAATs) within community-based case finding (CBCF) strategies. Although World Health Organization (WHO) recommends wider access to molecular testing, its use remains concentrated in facility-based settings well short of the global targets and largely dependent on sputum production. This creates a substantial diagnostic gap for people reached through community screening who either cannot provide sputum or whose sputum specimens cannot be tested on a NAAT at a facility, particularly for marginalized, hard-to-reach populations with poor access to healthcare.

Подробное описание

By embedding NPOC swab testing into CBCF strategies in Bangladesh, Cameroon, and Nigeria, this study will generate:

* Diagnostic accuracy estimates for NPOC among adults ≥15 years and young adolescents (10-14 years) identified through lung health camps after screening with CAD CXR-AI. * Direct evidence on NPOC use in non-sputum producers in community settings, addressing one of the most pressing gaps highlighted by WHO and national TB programmes. * Feasibility and acceptability insights on integrating NPOC into CBCF algorithms, complementing existing facility-based evidence. * Cost and cost-effectiveness estimate of using NPOC in CBCF.

The findings will directly support future WHO guideline development and inform national programme decisions on incorporating NPOC assays into CBCF models to reach populations at greatest risk of being missed by sputum-based approaches.

Вмешательства

• Диагностический тест Near point of care (NPOC) NAATs
  * Near point of care instrument that can test tongue swabs and sputum swabs\[6\]. * Rapid molecular detection system for detecting infectious diseases included TB, able to provide accurate test results that are comparable to top laboratory PCR tests, while it is easier to sue and move around and only takes 15 to 35 minutes to conclude the result. * Sample: Tongue swab or sputum swab (when sputum can be produced). * Processed directly on the near point-of-care device. * Results will be autom
• Диагностический тест Low-complexity nucleic acid amplification tests (LC-NAATs)
  * Semi-quantitative, nested real-time polymerase chain reaction (PCR) diagnostic test for the detection of Mycobacterium tuberculosis (MTB) complex DNA in unprocessed sputum samples\[9, 10\]. It can also detect rifampicin-resistance associated mutations in MTB. Results are automatically displayed on the screen of the system in less than 80 minutes. * Sample: Performed on sputum specimens where sputum can be produced. * Results are available within 1-2 days depending on site capacity. Reported ba
• Диагностический тест LC-NAAT using pooled testing
  Platform available at the health facility will be used to perform pooled testing (4, 8, 16 or 32 modules). Sample/Procedure: Pooled testing involves combining equal volumes from multiple individuals' samples and testing them together using a single test\[10\]. Pools will be created using remaining samples from 2-4 participants who have screened positive and were able to produce a sputum, guided by CAD CXR-AI thresholds\[11\]. To the possible extend, pools will be suggested by CAD band score: 0.
• Диагностический тест Computer-Aided Detection (CAD) Chest X-ray (CXR-AI)
  Computer-aided detection (CAD) software for chest X-rays is designed to support rapid, automated screening for tuberculosis and other thoracic abnormalities. Operating on mobile or computer platforms, these tools can analyse chest X-rays in less than a minute, distinguishing normal from abnormal scans and highlighting findings in the lungs, pleura, mediastinum, bones, diaphragm, and heart. In addition to detecting disease, some systems can assist clinicians with tasks such as verifying device pl
• Диагностический тест Culture (reference standard)
  The Mycobacterial Culture (solid or liquid, depending on country platform availability) is the gold-standard diagnostic test for tuberculosis. Culture detects viable Mycobacterium tuberculosis (MTB) organisms by growing them on selective media, allowing for confirmation of disease and, where relevant, downstream drug susceptibility testing (DST). Sample: Performed on sputum specimens where sputum can be produced. Turnaround time: Results are typically available within 2-8 weeks depending on the
• Диагностический тест Sputum smear microscopy
  Sputum smear microscopy (Ziehl-Neelsen or fluorescent staining, depending on laboratory platform availability) is a conventional diagnostic method that detects Mycobacterium tuberculosis (MTB) through visualisation of acid-fast bacilli (AFB) under a microscope. While widely used, its sensitivity is limited, particularly in individuals with paucibacillary disease or those unable to produce quality sputum. Sample: Performed on sputum specimens where sputum can be produced. Turnaround time: As mi

Первичные конечные точки

• Primary Endpoint: Diagnostic accuracy (sensitivity, specificity, PPV, NPV) of NPOC assays (tongue swab and sputum swab) compared against the microbiological reference standard (MRS: sputum culture). [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]

Вторичные конечные точки (9)

• Secondary Endpoint 1: Diagnostic Yield among Non-Sputum Producers and people with difficulty to produce sputum [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]
• Secondary Endpoint 2: cost and cost-effectiveness of NPOC diagnostics in community-based case-finding (CBCF) setting and diagnostic algorithms among adults (15 years and above) and young adolescents (10-14 years) [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]
• Secondary Endpoint 3.1: Feasibility & acceptability of NPOC from the perspective of people reached through CBCF and from the health system. [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]
• Secondary Endpoint 3.1: Feasibility & acceptability of NPOC from the perspective of people reached through CBCF and from the health system. [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]
• Secondary Endpoint 3.2: Feasibility & acceptability of NPOC from the perspective of people reached through CBCF and from the health system. [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]
• Secondary Endpoint 3.3: Feasibility & acceptability of NPOC from the perspective of people reached through CBCF and from the health system. [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]
• Secondary Endpoint 4.1: Diagnostic yield of TB among participants using self-collected swabs compared with HCW-collected swabs [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]
• Secondary Endpoint 4.2: Diagnostic accuracy of self-collected tongue swabs [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]
• Secondary Endpoint 4.3: Diagnostic accuracy of HCW-collected tongue swabs [Срок оценки: The overall duration of the DARE-TB Study is expected to be 12 months, beginning in Q2 2026 and concluding in Q2 2027. Recruitment, diagnostic testing, and follow-up will all occur between Q2 2026 and Q1 2027]

Критерии участия

Критерии включения

• Age:

• Adults aged 15 years and above
• Young adolescents aged 10-14 years
• Community setting:

o Rural and urban poor, elderly, marginalized groups, internally displaced persons (IDP) in camps and host communities, nomadic communities, and contacts of people with TB who attend community-based case finding (CBCF) campaigns.

• Screening eligibility:

• Screen positive on CAD CXR-AI (CAD score threshold ≥ 0.3).
• Consent:

• Written informed consent (and assent for adolescents if recruited) must be obtained according to local ethics and regulatory requirements.

Критерии исключения

• Age o Below 10 years at enrolment
• Screening eligibility

o Do not screen positive with CAD CXR-AI (CAD score threshold <0.3).

• Consent and follow-up

o Unable or unwilling to provide written informed consent (and assent where applicable) or unwilling to agree to follow-up visits.

• Current TB treatment

o Receiving anti-TB treatment at the time of enrolment, defined as having taken ≥3 doses of TB treatment.

• Recent TB preventive therapy

o Receipt of TB preventive therapy within the last 6 months prior to enrolment.

• Clinical danger signs

o Presence of severe illness at screening, including but not limited to:

▪ Respiratory rate >30/min St

• Fever >39°C
• Pulse rate >120/min
• Inability to walk unaided
• Duplicate enrolment o Previous enrolment in DARE-TB.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Azam K, Cadir N, Madeira C, Gillespie SH, Sabiiti W. OMNIgene.SPUTUM suppresses contaminants while maintaining Mycobacterium tuberculosis viability and obviates cold-chain transport. ERJ Open Res. 2018 Feb 16;4(1):00074-2017. doi: 10.1183/23120541.00074-2017. eCollection 2018 Jan. PMID 29479537
• Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF; STARD Group. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015 Oct 28;351:h5527. doi: 10.1136/bmj.h5527. PMID 26511519
• Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res. 2017 Jan 26;17(1):88. doi: 10.1186/s12913-017-2031-8. PMID 28126032
• French SD, Green SE, O'Connor DA, McKenzie JE, Francis JJ, Michie S, Buchbinder R, Schattner P, Spike N, Grimshaw JM. Developing theory-informed behaviour change interventions to implement evidence into practice: a systematic approach using the Theoretical Domains Framework. Implement Sci. 2012 Apr 24;7:38. doi: 10.1186/1748-5908-7-38. PMID 22531013
• Barker PM, Reid A, Schall MW. A framework for scaling up health interventions: lessons from large-scale improvement initiatives in Africa. Implement Sci. 2016 Jan 29;11:12. doi: 10.1186/s13012-016-0374-x. PMID 26821910
• Klaic M, Kapp S, Hudson P, Chapman W, Denehy L, Story D, Francis JJ. Implementability of healthcare interventions: an overview of reviews and development of a conceptual framework. Implement Sci. 2022 Jan 27;17(1):10. doi: 10.1186/s13012-021-01171-7. PMID 35086538
• Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30. PMID 18929686
• Datta S, Shah L, Gilman RH, Evans CA. Comparison of sputum collection methods for tuberculosis diagnosis: a systematic review and pairwise and network meta-analysis. Lancet Glob Health. 2017 Aug;5(8):e760-e771. doi: 10.1016/S2214-109X(17)30201-2. Epub 2017 Jun 15. PMID 28625793

Идентификаторы

NCT: NCT07420881 · 124

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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