Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis
背景
含利福喷丁方案具有很强的抗分枝杆菌活性，因此我们可能可以缩短药物敏感性肺结核患者的疗程。
Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis.
在对13个国家的新诊断肺结核患者开展的开放标签、3期、随机、对照试验中，我们采用6.6个百分点的非劣效性界值比较了两种4个月含利福喷丁方案和标准6个月方案（包括利福平、异烟肼、吡嗪酰胺和乙胺丁醇）（对照）。在一种4个月方案中，利福平被利福喷丁取代；在另一种方案中，利福平被利福喷丁取代，而乙胺丁醇被莫西沙星取代。主要疗效结局是12个月时的无结核病生存。
In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months.
在接受随机分组的2516例参与者中，2343例的培养结果显示对异烟肼、利福平或氟喹诺酮类不耐药的结核分枝杆菌阳性（符合微生物学标准的人群；对照组768例，利福喷丁-莫西沙星组791例，利福喷丁组784例），其中194例合并感染人类免疫缺陷性病毒，1703例的胸片可见空洞形成。共计2234例参与者的主要结局可评估（可评估的人群；对照组726例，利福喷丁-莫西沙星组756例，利福喷丁组752例）。在符合微生物学标准的人群（15.5% vs. 14.6%有不良结局；差异，1.0个百分点；95%置信区间[CI]，-2.6~4.5）和可评估的人群（11.6% vs. 9.6%；差异，2.0个百分点；95% CI，-1.1~5.1）中，利福喷丁+莫西沙星均不劣于对照。次要和敏感性分析也证明了非劣效性。在任一人群中，不含莫西沙星的利福喷丁方案均未被证明不劣于对照（在符合微生物学标准的人群中，17.7% vs. 14.6%有不良结局；差异，3.0个百分点[95% CI，-0.6~6.6]；在可评估的人群中，14.2% vs. 9.6%；差异，4.4个百分点[95% CI，1.2~7.7]）。在治疗期间，对照组19.3%的参与者、利福喷丁-莫西沙星组18.8%的参与者和利福喷丁组14.3%的参与者发生了3级或更高级别的不良事件。
Result
Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine–moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine–moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], −2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, −1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, −0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine–moxifloxacin group, and 14.3% in the rifapentine group.
结论
在结核病治疗中，含莫西沙星的4个月利福喷丁方案不劣于标准6个月方案。（由美国疾病控制与预防中心等资助；研究31/A5349在ClinicalTrials.gov注册号为NCT02410772。）
Conclusions
The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.)
Susan E. Dorman, Payam Nahid, Ekaterina V. Kurbatova, et al. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. DOI: 10.1056/NEJMoa2033400
