■全球,在研究开始期间,没有关于10mg/kg和25/35mg/kg利福平治疗肺结核的头对头比较的试验数据.
■多中心,IIb期随机试验招募了333名新的培养阳性,对药物敏感的成人肺结核患者,比较大剂量利福平(R25/R35)的安全性和有效性,与常规剂量(R10)相比,每天给予8周,然后标准剂量16周。主要结果是治疗引起的3/4级不良事件(AE)和液体培养基中的培养时间转换,通过对AIDS不良事件的严重程度进行划分评估的系统划分标准和Kaplan-Meier方法。
■在323名患者的改良意向治疗人群中(R10:105/R25:112/R35:106),34例患者报告了3/4级不良事件(R10:9.5%[10/105],R25:9.8%[11/112],R35:12.3%[13/106])在密集阶段。在23例患者中(R10:3.8%[4/105],R25:6.3%[7/112],R35:11.3%[12/106]),具有3/4级肝毒性,15(R10:1.9%[2/105],R25:3.6%[4/112],R35:8.5%[9/106])患有3/4级高胆红素血症和9例患者(R10:1.0%[1/105],R25:0.9%[1/112],R35:6.6%[7/106])出现临床黄疸。仅在具有肝毒性的R10和R35之间观察到显着差异(P=0.039),高胆红素血症(P=0.031),临床黄疸(P=.032),和治疗中断(P=0.039)。在研究期间发生18例严重AE和6例死亡(R10:3/R25:1/R35:2)。在R25中,液体培养基中稳定培养物转化的时间更快(调整后的危险比,1.71;95%置信区间[CI],1.26-2.31[固体:1.97;95%CI,1.46-2.67])和R35(1.81;95%CI,1.33-2.48[固体:2.24;95%CI,1.64-3.06]),比R10(34对44天)。R25没有失败/复发。
■肝毒性,临床黄疸,R35的治疗中断明显高于R10。因为R25与R10相比是比较安全的,并且也比R10高度有效,所以可以考虑实施。临床试验注册。CTRI/2017/12/010951。
UNASSIGNED: Globally, no
trial data are available on head-to-head comparison between 10 mg/kg and 25/35 mg/kg
rifampicin in treating pulmonary tuberculosis during
study initiation.
UNASSIGNED: A multicentric, phase IIb randomized
trial recruited 333 new culture-positive, drug-sensitive adult patients with pulmonary tuberculosis to compare safety and efficacy of high-dose
rifampicin (R25/R35), against conventional dose (R10) given daily for 8 weeks followed by standard doses for 16 weeks. Main outcomes were treatment-emergent grade 3/4 adverse events (AEs) and time-to-culture conversion in liquid media, assessed by division of AIDS system for grading the severity of adverse events division of AIDS criteria and Kaplan-Meier methods.
UNASSIGNED: In a modified intention-to-treat population of 323 patients (R10: 105/R25: 112/R35: 106), grade 3/4 AEs were reported in 34 patients (R10: 9.5% [10/105], R25: 9.8% [11/112], R35: 12.3% [13/106]) during the intensive phase. Among 23 patients (R10: 3.8% [4/105], R25: 6.3% [7/112], R35: 11.3% [12/106]) with grade 3/4 hepatotoxicity, 15 (R10: 1.9% [2/105], R25: 3.6% [4/112], R35: 8.5% [9/106]) had grade 3/4 hyperbilirubinemia and 9 patients (R10: 1.0% [1/105], R25: 0.9% [1/112], R35: 6.6% [7/106]) developed clinical jaundice. Significant differences observed only between R10 and R35 with hepatotoxicity (P = .039), hyperbilirubinemia (P = .031), clinical jaundice (P = .032), and treatment interruption (P = .039). Eighteen serious AEs and 6 deaths (R10: 3/R25: 1/R35: 2) occurred during
study period. Time to stable culture conversion in liquid media was faster in R25 (adjusted hazard ratio, 1.71; 95% confidence interval [CI], 1.26-2.31 [solid: 1.97; 95% CI, 1.46-2.67]) and R35 (1.81; 95% CI, 1.33-2.48 [solid: 2.24; 95% CI, 1.64-3.06]), than R10 (34 vs 44 days). R25 had no failure/relapse.
UNASSIGNED: Hepatotoxicity, clinical jaundice, and treatment interruptions occurred significantly higher with R35 than R10. Because R25 was comparably safe as R10 and also highly efficacious than R10, it may be considered for implementation. Clinical Trials Registration. CTRI/2017/12/010951.