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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
3,520
12-dose ultra-short TPT 1H3P3 regimen of isoniazid and rifapentine 3 times a week for 4 weeks
3HR regimen of isoniazid and rifampicin once daily for three months
Cumulative incidence of active tuberculosis (TB) over 24 months
The primary endpoint is a composite of bacteriologically confirmed or clinically diagnosed active TB within 24 months after randomization. Bacteriologically confirmed TB is defined as M. tuberculosis detection by sputum culture and/or molecular assay (e.g., GeneXpert MTB/RIF). Clinically diagnosed TB requires the presence of ≥2 objective clinical symptoms (cough ≥2 weeks, fever, night sweats, weight loss \>10%, or hemoptysis) plus chest imaging findings highly suggestive of active TB, after exclusion of alternative diagnoses. This measure will be used to assess the non-inferiority of the 1H3P3 regimen compared to the 3HR regimen.
Time frame: up to 24 months after randomization
Proportion of participants with adverse events (AEs) and serious adverse events (SAEs)
To compare the safety profiles between the 1H3P3 and 3HR regimens. All AEs and SAEs will be documented, and group differences in AE proportions will be analyzed. Severity will be graded per the Division of AIDS (DAIDS) table.
Time frame: from first dose to one month after treatment completion
Incidence of treatment discontinuation attributable to AEs
To compare the treatment discontinuation rates due to AEs between the 1H3P3 and 3HR regimens
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.
Defined as the proportion of participants who complete ≥90% of scheduled doses within 110% of the planned treatment duration (≥11 doses within 6 weeks for 1H3P3 group and ≥81 doses within 16 weeks for 3HR group)
Time frame: up to 16 weeks from randomization
All-cause mortality.
Death from any cause during the 24-month follow-up period.
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People's Hospital of Ziyun
Anshun, Guiyang, China
RECRUITINGPeople's Hospital of Guanling
Anshun, Guizhou, China
RECRUITINGPeople's Hospital of Pingba District
Anshun, Guizhou, China
RECRUITINGPeople's Hospital of Puding
Anshun, Guizhou, China
RECRUITINGPeople's Hospital of Xixiu District
Anshun, Guizhou, China
RECRUITINGPeople's Hospital of Zhenning
Anshun, Guizhou, China
RECRUITINGPeople's Hospital of Hezhang
Bijie, Guizhou, China
RECRUITINGPeople's Hospital of Qianxi
Bijie, Guizhou, China
RECRUITINGPeople's Hospital of Qianxi
Bijie, Guizhou, China
RECRUITINGPeople's Hospital of Weining
Bijie, Guizhou, China
RECRUITING...and 56 more locations
Time frame: up to 24 months after randomization
Acquired drug resistance
The proportion of participants who develop active TB post-TPT and whose M. tuberculosis isolate shows resistance to isoniazid, rifampicin, or rifapentine by drug susceptibility testing or targeted molecular assays.
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
To establish the background incidence of active TB among high-risk LTBI individuals who declined TPT, and to quantify the risk reduction rate (protective efficacy) of the 1H3P3 and 3HR regimens relative to this non-intervention cohort. Risk reduction rate = 1-(intervention group incidence / nonintervention group incidence)
Time frame: From enrollment up to 24 months.