Clinical trial NCT06022146: TB YOUTH - TB sYstemic Management Using One-month, Ultra-short TPT Regimen for scHool Contacts
Official title: TB YOUTH - TB sYstemic Management Using One-month, Ultra-short TPT Regimen for scHool Contacts
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Tuberculosis
Latent Tuberculosis
Keywords: latent tuberculosis
TPT
active screening
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2023-09-01
Enrollment: 2978
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female, ≥13 years old, weighting ≥30kg;
2. Students of junior middle school, high school or college, or school staff;
3. In the scope of ATB case-driven screening delimited by local CDC;
4. Positive in IGRA test and diagnosed as LTBI;
5. Voluntary (together with his/her guardian for age under 18 years old) participant in trial and signed 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.

Primary outcomes:
measure: Number of participants with culture or GeneXpert MTB/RIF confirmed TB or clinically highly suggested TB
timeFrame: up to 24 months after randomization
Secondary outcomes:
measure: Number of participants permanently withdrawal from medication for any reason.
timeFrame: up to 24 months after randomization
measure: N Number of participants complete the treatment.
timeFrame: up to 24 months after randomization
measure: All-cause mortality.
timeFrame: up to 24 months after randomization
measure: Number of participants with drug resistance result.
timeFrame: up to 24 months after randomization
Other outcomes:
Locations:
city: Bijie
country: China
facility: People's Hospital of Hezhang
state: Guizhou
city: Bijie
country: China
facility: People's Hospital of Qianxi
state: Guizhou
city: Bijie
country: China
facility: People's Hospital of Weining
state: Guizhou
city: Bijie
country: China
facility: People's Hospital of Zhijin
state: Guizhou
city: Bijie
country: China
facility: People's Hospital of Zhijin
state: Guizhou
city: Daozhen Klau and Hmong autonomous county in Zun'yi
country: China
facility: People's Hospital of Daozhen Klau and Hmong autonomous county
state: Guizhou
city: Liupanshui
country: China
facility: Liuzhi Special District
state: Guizhou
city: Liupanshui
country: China
facility: People's Hospital of Panzhou
state: Guizhou
city: Liupanshui
country: China
facility: People's Hospital of Shuicheng District, Liupanshui City
state: Guizhou
city: Liupanshui
country: China
facility: Second People's Hospital of Liupanshui City
state: Guizhou
city: Liupanshui
country: China
facility: Third People's Hospital of Liupanshui
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Prefecture
country: China
facility: People's Hospital of Cengong
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Prefecture
country: China
facility: People's Hospital of Congjiang
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: First People's Hospital of Kaili
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Danzhai
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Huangping
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Jianhe
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Jinping
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Liping
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Rongjiang
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Sansui
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Shibing
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Tianzhu
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Zhenyuan
state: Guizhou
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: Poeple's Hospital of Leishan
state: Guizhou
city: Zunyi
country: China
facility: Guizhou Aerospace Hospital
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Bozhou District
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Chishui
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Fenggang
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Honghuagang District
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Meitan
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Renhuai
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Suiyang
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Tongzi
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Wuchuan Klau and Hmong autonomous county
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Xishui
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Yuqing
state: Guizhou
city: Zunyi
country: China
facility: People's Hospital of Zhengan
state: Guizhou
city: Zunyi
country: China
facility: Zunyi Infectious Disease Hospital
state: Guizhou
city: Dalian
country: China
facility: Dalian Public Health Clinical Center
state: Liaoning
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
city: Bijie
country: China
facility: 3rd People's Hospital of Bijie
city: Bijie
country: China
facility: People's Hospital of Dafang Town
city: Bijie
country: China
facility: People's Hospital of Nayong
city: Guiyang
country: China
facility: Chinese Medicine Hospital of Qingzhen
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Majiang
city: Qiandongnan Miao and Dong Autonomous Region
country: China
facility: People's Hospital of Taijiang
Study officials:
References: