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

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.

Study Overview

• Status: Recruiting
• Conditions: Latent Tuberculosis; Tuberculosis
• Intervention / Treatment: Drug: Rifampin and Isoniazid; Drug: isoniazid and rifapentine

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, the study will need 1658 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 Type: Interventional
• Enrollment (Estimated): 3520
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ruan Qiaoling, PhD; Phone Number: 13661856002; Email: ruan_qiao_ling@fudan.edu.cn
• Study Contact Backup: Name: Zhang Wenhong, PhD; Phone Number: 52888123; Email: zhangwenhong@fudan.edu.cn

Study Locations

• China
  • Bijie, China
    • Recruiting
    • 3rd People's Hospital of Bijie
    • Contact: Lijuan Lin
  • Bijie, China
    • Recruiting
    • People's Hospital of Dafang Town
    • Contact: Zhengjie Jiang
  • Bijie, China
    • Recruiting
    • People's Hospital of Nayong
    • Contact: Qili Liu
  • Guiyang, China
    • Recruiting
    • Chinese Medicine Hospital of Qingzhen
    • Contact: Jie Yang
  • Guizhou
    • Autonomous Region, Guizhou, China
      • Recruiting
      • People's Hospital of Liping Town
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Central Hospital of Jingan District
      • Contact: Wenhong Zhang, Prof; Phone Number: 021-61578000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Students of junior middle school, high school and university, age13 years old
2. Close contact of school active tuberculosis case (e.g. in the same classroom, in the same dormitory, in the same floor)
3. IGRA (Interferon-Gamma Release Assay) is positive and diagnosed as LTBI
4. Himself/herself (together with his/her guardian for age under 18 years old) willing to participate in trial and sign informed consent.

Exclusion Criteria:

1. Current clinical or sputum culture confirmed active tuberculosis
2. Had continuously taken rifamycin (rifampicin, rifapentine etc.) or isoniazid for more than 14 days in the past 2 years
3. Have completed a full course of treatment for ATB or LTBI
4. Allergic or intolerant to rifamycin (rifapentine or rifampicin) or isoniazid
5. HIV (human immunodeficiency virus) antibody positive or AIDS (Acquired immunodeficiency syndrome) patients
6. History of viral hepatitis (e.g. chronic hepatitis B, chronic hepatitis C) or liver cirrhosis
7. Liver dysfunction (Total bilirubin > 5mg/dL (43 umol/L) or Alanine aminotransferase > 2ULN or Aspartate aminotransferase > 2ULN) or renal dysfunction
8. Current receiving immunosuppressive therapy or biological agents
9. Blood system diseases or Platelet count<50×10^9/L or White Blood Cell count<3.0×10^9/L
10. Other conditions deemed unsuitable for TPT by physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1H3P3 regimen of isoniazid and rifapentine 3 times a week for one month; 12-dose ultra-short TPT 1H3P3 regimen of isoniazid and rifapentine 3 times a week for one month	Drug: Rifampin and Isoniazid; 3HR regimen of isoniazid and rifampicin once daily for three months
Active Comparator: 3HR regimen of isoniazid and rifampicin once daily for three months	Drug: isoniazid and rifapentine; 12-dose ultra-short TPT 1H3P3 regimen of isoniazid and rifapentine 3 times a week for one month

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: March 23, 2023
• First Submitted That Met QC Criteria: August 28, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Actual): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: latent tuberculosis; TPT; active screening
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Tuberculosis; Latent Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Fatty Acid Synthesis Inhibitors; Rifapentine; Rifampin; Isoniazid
• Other Study ID Numbers: KY-2023-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This research targets adolescent students in school. We decide not to share IPD from the ethical perspective.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No