Single-Dose Rifapentine in Household Contacts of Patients with Leprosy
Le Wang, Hongsheng Wang, Liangbin Yan, et al
N Engl J Med 2023; 388:1843-1852
DOI: 10.1056/NEJMoa2205487
Abstract
BACKGROUND
Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking.
背景
之前的研究提示，在麻风的密切接触者中，单剂量利福平有保护作用，可预防麻风。在麻风小鼠模型中，利福喷丁对麻风分枝杆菌的杀菌活性超过利福平，但目前缺乏关于其预防麻风的有效性数据
METHODS
We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts.
方法
我们开展了一项整群随机对照试验，研究单剂量利福喷丁对麻风家内接触者的是否有预防作用。整群（中国西南地区的县或区）被分配到以下三个试验组之一：单剂量利福喷丁、单剂量利福平或对照（无干预）。主要结局是家内接触者中麻风的4年累积发病率。
RESULTS
A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P=0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P=0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed.
结果
共207个群（包括7450名家内接触者）被随机分组；68个群（2331名家内接触者）被分配到利福喷丁组，71个群（2760名）被分配到利福平组，68个群（2359名）被分配到对照组。4年随访期间共有24例麻风新发病例，在利福喷丁组（2例）、利福平组（9例）和未干预组（13例）中，累积发病率分别为0.09%（95%置信区间[CI]，0.02~0.34）、0.33%（95% CI，0.17~0.63）和0.55%（95% CI，0.32~0.95）。在意向性治疗分析中，利福喷丁组的累积发病率比对照组低84%（累积发病率比，0.16；经多重校正的95% CI，0.03~0.87；P=0.02）；利福平组和对照组的累积发病率无显著差异（累积发病率比，0.59；经多重校正的95% CI，0.22~1.57；P=0.23）。在符合方案分析中，在利福喷丁组、利福平组和无干预组中，累积发病率分别为0.05%、0.19%和0.63%。未观察到严重不良事件。
CONCLUSIONS
The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075. opens in new tab.)
结论
在接受单剂量利福喷丁治疗的家内接触者中，4年期间的麻风发病率低于未接受干预的家内接触者。（由中国国家卫生健康委员会和中国医学科学院资助；中国临床试验注册中心注册号为ChiCTR-IPR-15007075）。
