Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and Assessing Diagnostics At POC for TB in Children (ADAPT for Kids)

Официальное название

Rapid Research in Diagnostics Development for Tuberculosis Network (R2D2 Kids) and Assessing Diagnostics At Point-of-care for Tuberculosis in Children (ADAPT for Kids)

Обзор

Every year there are an estimated 230,000 childhood deaths from TB. There is an urgent need for novel tests for TB diagnosis in children under 15 years. The Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and the Assessing Diagnostics at Point-of-care for Tuberculosis in children (ADAPT for Kids) studies seek to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests for use in children.

Подробное описание

The Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and the Assessing Diagnostics at Point-of-care for Tuberculosis in children (ADAPT for Kids) studies will rigorously assess promising, point-of-care (POC) TB diagnostic tests in clinical studies conducted among children at settings of intended use. There is an urgent need for novel tests for TB diagnosis in children under 15 years because of the challenge of obtaining sputum samples from children and the low sputum bacillary burden among children with TB even when a sample is obtained. This creates delays in diagnosis and treatment initiation, and is a major contributor to the 230,000 childhood deaths from TB each year. Therefore, a non-sputum biomarker-based test has been ranked among the highest priority target product profiles for new TB diagnostics. If inexpensive and simple to perform, such a diagnostic tool could have significant impact by facilitating rapid diagnosis and TB treatment in children. The studies will evaluate the sensitivity and specificity of novel diagnostic tests in children in reference to NIH consensus definitions for childhood TB. In addition, the usability and acceptability of the novel TB diagnostic tests will be assessed through direct observations and surveys of routine health workers.

Вмешательства

• Диагностический тест Oral swab molecular testing
  Swab-based testing provides a non-invasive approach to collect respiratory specimens for TB testing. Data in adults suggests that swab-based testing could be valuable when sputum collection is not feasible or available.
• Диагностический тест Automated Cough Sound Analysis
  Cough sounds can be collected through a mobile phone and tablet, and then analyzed with machine learning algorithms to predict TB.
• Диагностический тест Automated Lung Sound Analysis
  Lung sounds can be collected with a non-invasive digital stethoscope, and then saved on a tablet or phone and analyzed by machine learning algorithms to predict TB.
• Другое Chest X Ray Computer Aided Detection
  Several artificial intelligence algorithms have been developed to predict TB, though this has not yet been validated in children.

Первичные конечные точки

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

Критерии участия

Participant eligibility criteria:

Participants will include children (age <15 years) who present to care with:

A. 2 or more of the following:

• Unexplained cough for any duration
• TB contact or tuberculin skin test or interferon gamma release assay positive
• Abnormal chest X-ray (any abnormality) OR

B. Any one of criteria A AND any one of the following:

• Unexplained weight loss OR unexplained failure to thrive OR Severe Acute Malnutrition
• Unexplained fever ≥2 weeks
• Unexplained lethargy or reduced playfulness ≥2 weeks

The study will exclude participants who:

• Completed preventive 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 for any reason for greater than 3 days at the time of enrollment (to reduce false-negatives);
• Are unable to return for follow-up visits; or
• Whose parents/guardians are unwilling to provide informed consent or who are unwilling to provide assent if applicable (age determined by local IRB)

Assessment of the usability of novel TB tests:

The study will also 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). Personnel who are unwilling to provide informed consent will be excluded.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Mozambique · 1 центр

• Instituto Nacional de Saúde — Maputo

ЮАР · 1 центр

• Dora Nginza Hospital — Cape Town

Uganda · 1 центр

• Mulago National Referral Hospital — Kampala

Публикации

• Perez-Velez CM, Marais BJ. Tuberculosis in children. N Engl J Med. 2012 Jul 26;367(4):348-61. doi: 10.1056/NEJMra1008049. No abstract available. PMID 22830465
• World Health Organization. Roadmap towards ending TB in children and adolescents. Geneva: World Health Organization, 2018. Available at: https://www.who.int/tb/publications/2018/tb-childhoodroadmap/en/. Last accessed 1 June 2022.
• WHO. High-priority target product profiles for new tuberculosis diagnostics: Report of a consensus meeting. Geneva, Switzerland. Available at: http://www.who.int/tb/publications/tpp_report/en/, 2014.
• Graham SM, Cuevas LE, Jean-Philippe P, Browning R, Casenghi M, Detjen AK, Gnanashanmugam D, Hesseling AC, Kampmann B, Mandalakas A, Marais BJ, Schito M, Spiegel HM, Starke JR, Worrell C, Zar HJ. Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children: An Update. Clin Infect Dis. 2015 Oct 15;61Suppl 3(Suppl 3):S179-87. doi: 10.1093/cid/civ581. PMID 26409281
• World Health Organization. Global Tuberculosis Report 2021. Geneva: World Health Organization, 2021.
• World Health Organization. Roadmap towards ending TB in children and adolescents. Geneva: World Health Organization, 2018.
• Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, Keane J, Lewinsohn DA, Loeffler AM, Mazurek GH, O'Brien RJ, Pai M, Richeldi L, Salfinger M, Shinnick TM, Sterling TR, Warshauer DM, Woods GL. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Child PMID 28052967
• WHO consolidated guidelines on tuberculosis: Module 5: Management of tuberculosis in children and adolescents [Internet]. Geneva: World Health Organization; 2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK579387/ PMID 35404556

Идентификаторы

NCT: NCT05989802 · R01HL169449 · U01AI152087 · 7200AA22RFA00004

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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