A Novel Therapy With a 1-Month Ultrashort Regimen to Halt Progression From Latent Infection to Active Tuberculosis Among Close Contacts (The TB-YOUTH Study)

Обзор

This is a prospective, multi-center, open-label, cluster randomized controlled clinical trial conducted in school settings to estimate the non-inferiority effect of 1H3P3 compared with 3HR.

Подробное описание

Background： Adolescents are susceptible to tuberculosis. Almost 1.1 million children (aged below 15 years) and another half a million older adolescents (15-19 years) become ill with TB every year. Approximately 5%-10% people infected with TB develop to active disease, which suggest that a great proportion of adolescents remain undiagnosed and unprotected. Undiagnosed cases and school-based transmission contribute to the burden of TB among adolescents. Closing the gap in targeted interventions for TB prevention in schools is essential to break the cycle of transmission and ensure the well-being of school-aged adolescents. However, TB preventive treatment targeted on adolescents are still lacking.

Method： This is a prospective, multicenter, open-label, non-inferiority, cluster randomized controlled clinical trial within the national tuberculosis control program of GuiZhou,China. Close contacts of school tuberculosis index cases are actively screened with QFT(QuantiFERON-TB Gold Plus), chest X-ray, pooled GeneXpert MTB/RIF test of sputum and symptoms. After ruling out active tuberculosis, LTBI students are enrolled to attend a non-inferiority, cluster randomized controlled clinical trial. The students will be given either 3HR or 1H3P3 regimen and followed for two years. Our primary endpoint is culture or GeneXpert MTB/RIF confirmed TB or clinically highly suggested TB. Assume ICC (interclass correlation coefficient) to be 0.05, and the the lost to follow-up rate is 10%, the study will need 1760 subjects per arm to provide 80% power to detect a 20% non-inferiority margin of primary endpoint between the two arms.

Discussion:

The effectiveness of contact investigation among adolescent students as a tool for improved tuberculosis control has not been established. The integration of ultra-short treatment regimens with active screening holds the potential to provide a comprehensive and effective strategy for tuberculosis prevention and control in school environments, which may help reform the national tuberculosis policy regarding adolescent TB.

Вмешательства

• Препарат isoniazid and rifapentine
  12-dose ultra-short TPT 1H3P3 regimen of isoniazid and rifapentine 3 times a week for 4 weeks
• Препарат Rifampin and Isoniazid
  3HR regimen of isoniazid and rifampicin once daily for three months

Первичные конечные точки

• Cumulative incidence of active tuberculosis (TB) over 24 months [Срок оценки: up to 24 months after randomization]

Вторичные конечные точки (6)

• Proportion of participants with adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: from first dose to one month after treatment completion]
• Incidence of treatment discontinuation attributable to AEs [Срок оценки: During the treatment course period (up to 1 month for 1H3P3 arm and up to 3 months for 3HR arm).]
• Treatment completion rate. [Срок оценки: up to 16 weeks from randomization]
• All-cause mortality. [Срок оценки: up to 24 months after randomization]
• Acquired drug resistance [Срок оценки: At time of active TB diagnosis, up to 24 months post-randomization.]
• 2-year cumulative incidence of active TB in the non-intervention cohort [Срок оценки: From enrollment up to 24 months.]

Критерии участия

Критерии включения

• Aged ≥13 years and body weight ≥ 30 kg;
• School-registered individuals including:

• Currently attending junior / senior high school or university students;
• School staff members;
• Close contacts of active pulmonary TB index cases (confirmed or clinically diagnosed) within the school, defined by meeting both of the following:

• Teachers/students sharing the same classroom or dormitory with the index case;
• Exposure history: Prolonged sharing of enclosed space (>4 hours total within 1 week) with the index case;
• Confirmed LTBI status through screening;
• Voluntary participation with signed informed consent form (for adults ≥18 years);
• Parental / guardian consent and co-signed informed consent form (for minors aged 13-17 years).

Критерии исключения

• Current active TB disease (clinically or bacteriologically confirmed);
• Documented isoniazid/rifampicin resistance in the corresponding M. tuberculosis strain from the index case;
• Self-reported use of rifamycins (e.g., rifampicin, rifapentine) or isoniazid for >14 consecutive days within the past 2 years;
• Prior completion of full-course of treatment for ATB or LTBI;
• Hypersensitivity or intolerance to rifamycins (rifapentine / rifampicin) or isoniazid;
• HIV positive serostatus or AIDS patients;
• History of viral hepatitis (e.g., chronic hepatitis B, chronic hepatitis C) or liver cirrhosis;
• Liver dysfunction (TBil>2.5mg/dL \[43umol/L\] or ALT / AST>2ULN) or renal dysfunction.
• Current receiving immunosuppressive therapy or biological agents.
• Hematologic disorders with either PLT<50×109/L or WBC<3.0×109/L.
• Other conditions deemed unsuitable for TPT by investigators.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Китай · 66 центров

• People's Hospital of Ziyun — Anshun
• People's Hospital of Guanling — Anshun
• People's Hospital of Pingba District — Anshun
• People's Hospital of Puding — Anshun
• People's Hospital of Xixiu District — Anshun
• People's Hospital of Zhenning — Anshun
• People's Hospital of Hezhang — Bijie
• People's Hospital of Qianxi — Bijie
• … и ещё 58 центров

Публикации

• Ruan QL, Yang QL, Ma CL, Lin MY, Huang XT, Mao YP, Gao JM, Li JJ, Zhang XN, You ZX, Zheng QQ, Ren YF, Liu XF, Shao LY, Zhang WH. Efficacy and safety of a novel short course rifapentine and isoniazid regimen for the preventive treatment of tuberculosis in Chinese silicosis patients: a pilot study (SCRIPT-TB). Emerg Microbes Infect. 2025 Dec;14(1):2502010. doi: 10.1080/22221751.2025.2502010. Epub 20 PMID 40326358

Идентификаторы

NCT: NCT06022146 · TB-YOUTH

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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