Matteelli Alberto, Russo Giulia, Rossi Luca, Cerini Carlo, Cimaglia Claudia, Formenti Beatrice, Dall'Asta Mirella, Cristini Irene, Gregori Natalia, Ghilardi Carlotta, Ciccarone Andrea, Previtali Letizia, Di Rosario Gianluca, Cirillo Daniela Maria, Girardi Enrico
Clinic of Infectious and Tropical Diseases, Department of Clinical and Experimental Sciences, WHO Collaborating Centre for Tuberculosis Infection, University of Brescia, Brescia, Italy.
Clinic of Infectious and Tropical Diseases, Department of Clinical and Experimental Sciences, WHO Collaborating Centre for Tuberculosis Infection, University of Brescia, Brescia, Italy.
Clin Microbiol Infect. 2025 Aug;31(8):1330-1335. doi: 10.1016/j.cmi.2025.02.037. Epub 2025 Mar 1.
Treatment of tuberculosis (TB) infection is a core intervention of the TB elimination strategy. The WHO recommends both 4 months of daily rifampicin (4R) and 3 months of daily isoniazid/rifampicin (3HR) for preventive therapy, but no trial directly compared the two regimens. We measured the completion rate and tolerability of 4R and 3HR for TB preventive therapy.
We conducted a prospective, open-label, randomized phase 4 superiority trial to demonstrate an increase of at least 15% in the completion rate of 4R over 3HR among asylum seekers in Italy. Asylum seekers were tested for TB infection by the Quantiferon Plus test and offered to participate in the study if infected. The primary outcome was treatment completion, measured by adherence to clinical visits and pill count. Unadjusted Kaplan-Meier curves were used to compare permanent interruptions in the two arms by days of treatment. Generalized linear model for the binomial family and logit link function was performed to determine factors associated with treatment completion.
From June 2021 to July 2023, we randomized 113 individuals to 4R and 112 to 3HR. Treatment was completed by 88 subjects (77.9; 95% CI, 69.1-85.1) in the 4R arm and 85 (75.9; 95% CI, 66.9-83.5) in the 3HR arm (p 0.7). The risk ratio for completing treatment was 1.03 (95% CI, 0.89-1.18) in the 4R arm compared with the 3HR arm with a risk difference of 0.03 (95% CI, -0.09 to 0.13). Dropout rates due to side effects (25/113 in 4R vs. 27/112 in 3HR) and the overall rate of adverse events (47/113 in 4R vs. 36/112 in 3HR) were not statistically different in the two groups.
4R was not superior, in terms of completion rate, to 3HR for the treatment of TB infection among asylum seekers in Italy.
EudraCT 2021-001438-20.
结核病（TB）感染治疗是结核病消除战略的核心干预措施。世界卫生组织推荐采用4个月每日服用利福平（4R）方案和3个月每日服用异烟肼/利福平（3HR）方案进行预防性治疗，但尚无试验直接比较这两种方案。我们测定了4R和3HR方案用于结核病预防性治疗的完成率和耐受性。
我们开展了一项前瞻性、开放标签、随机4期优效性试验，以证明在意大利的寻求庇护者中，4R方案的完成率比3HR方案至少高15%。采用QuantiFERON Plus检测法对寻求庇护者进行结核病感染检测，检测结果呈阳性者可参与本研究。主要结局为治疗完成情况，通过是否坚持门诊就诊和清点药丸数量来衡量。使用未调整的Kaplan-Meier曲线按治疗天数比较两组的永久性中断情况。采用二项式族广义线性模型和logit连接函数来确定与治疗完成相关的因素。
2021年6月至2023年7月，我们将113人随机分配至4R组，112人随机分配至3HR组。4R组有88名受试者（77.9%；95%CI，69.1%-85.1%）完成治疗，3HR组有85名（75.9%；95%CI，66.9%-83.5%）完成治疗（p=0.7）。与3HR组相比，4R组完成治疗的风险比为1.03（95%CI，0.89-1.18），风险差异为0.03（95%CI，-0.09至0.13）。两组因副作用导致的退出率（4R组为25/113，3HR组为27/112）和不良事件总发生率（4R组为47/113，3HR组为36/112）无统计学差异。
在意大利的寻求庇护者中，就完成率而言，4R方案在治疗结核病感染方面并不优于3HR方案。
EudraCT 2021-0
