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)

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (6)

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

Eligibility criteria

Inclusion criteria

• 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).

Exclusion criteria

• 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.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

China · 66 centers

• 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
• … and 58 more centers

Publications

• 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

Identifiers

NCT: NCT06022146 · TB-YOUTH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗