TB YOUTH - TB sYstemic Management Using One-month, Ultra-short TPT Regimen for scHool Contacts

Phase 3

Recruiting

• Conditions: Tuberculosis; Latent Tuberculosis
• Interventions: Drug: isoniazid and rifapentine; Drug: Rifampin and Isoniazid

• Registration Number: NCT06022146
• Lead Sponsor: Huashan Hospital

Brief Summary

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.

Study Timeline

• Study First Submitted: 2023-03-23
• Study First Submitted QC: 2023-08-28
• Study Start: 2023-09-01
• Study First Posted: 2023-09-01
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-13
• Last Update Posted: 2025-07-16
• Primary Completion: 2026-09-01
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2978

Inclusion Criteria

1. Aged ≥13 years and body weight ≥ 30 kg;

2. School-registered individuals including:

   • Currently attending junior / senior high school or university students;
   • School staff members;

3. 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;

4. Confirmed LTBI status through screening;

5. Voluntary participation with signed informed consent form (for adults ≥18 years);

6. Parental / guardian consent and co-signed informed consent form (for minors aged 13-17 years).

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3HR regimen of isoniazid and rifampicin once daily for three months	isoniazid and rifapentine	3HR regimen of isoniazid and rifampicin once daily for three months
1H3P3 regimen of isoniazid and rifapentine 3 times a week for one month	Rifampin and Isoniazid	12-dose ultra-short TPT 1H3P3 regimen of isoniazid and rifapentine 3 times a week for one month

Primary Outcome Measures

Name	Time	Method
Number of participants with culture or GeneXpert MTB/RIF confirmed TB or clinically highly suggested TB	up to 24 months after randomization	The primary aim is to estimate the effectiveness non-inferiority of 1H3P3 to 3HR.

Secondary Outcome Measures

Name	Time	Method
N Number of participants complete the treatment.	up to 24 months after randomization	to compare the completion rates of the two regimens
All-cause mortality.	up to 24 months after randomization	subjects may withdrawal from this study because of death
Number of participants with drug resistance result.	up to 24 months after randomization	to study drug resistance condition of school TB endemic
Number of participants permanently withdrawal from medication for any reason.	up to 24 months after randomization	subjects may withdrawal from medication after serious adverse effect

Trial Locations

Locations (46)

People's Hospital of Hezhang; 🇨🇳 Bijie, Guizhou, China

People's Hospital of Qianxi; 🇨🇳 Bijie, Guizhou, China

People's Hospital of Weining; 🇨🇳 Bijie, Guizhou, China

People's Hospital of Zhijin; 🇨🇳 Bijie, Guizhou, China

People's Hospital of Daozhen Klau and Hmong autonomous county; 🇨🇳 Daozhen Klau and Hmong autonomous county in Zun'yi, Guizhou, China

Liuzhi Special District; 🇨🇳 Liupanshui, Guizhou, China

People's Hospital of Panzhou; 🇨🇳 Liupanshui, Guizhou, China

People's Hospital of Shuicheng District, Liupanshui City; 🇨🇳 Liupanshui, Guizhou, China

Second People's Hospital of Liupanshui City; 🇨🇳 Liupanshui, Guizhou, China

Third People's Hospital of Liupanshui; 🇨🇳 Liupanshui, Guizhou, China

Scroll for more (36 remaining)