Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts
Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts
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DOI：
10.1056/nejmoa1915341
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发表时间：
2020-07-23
影响因子：
158.5
通讯作者：
Uehara, Takeki
中科院分区：
文献类型：
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作者：
Ikematsu, Hideyuki;Hayden, Frederick G.;Uehara, Takeki
在一项随机、双盲试验中，用单剂量baloxavir或安慰剂治疗流感患者的家庭接触者，服用baloxavir的参与者患流感的风险（1.9%）低于安慰剂对照组（13.6%）。Baloxavir marboxil（baloxavir）是一种聚合酶酸性蛋白（PA）内切酶抑制剂，在治疗无并发症的流感中具有临床疗效，包括在并发症风险增加的门诊患者中。方法我们进行了一项多中心、双盲、随机、安慰剂对照试验，以评估2018-2019年日本流感季期间，在确诊流感患者的家庭接触者中，baloxavir的治疗后预防效果。参与者按1：1的比例分配接受单剂量baloxavir或安慰剂。主要终点是临床流感，通过逆转录酶聚合酶链反应检测证实，为期10天。评估了与敏感性降低相关的巴洛沙韦选择性PA置换的发生。结果545名索引患者的752名家庭接触者被随机分配接受baloxavir或安慰剂。在索引患者中，95.6%有甲型流感病毒感染，73.6%年龄小于12岁，52.7%接受baloxavir。在可以评估的参与者中（baloxavir组374人，安慰剂组375人），baloxavir组发生临床流感的百分比显著低于安慰剂组（1.9% vs. 13.6%）（校正风险比，0.14; 95%置信区间[CI]，0.06 - 0.30; P
In a randomized, double-blind trial that treated household contacts of patients with influenza with a single dose of baloxavir or placebo, participants taking baloxavir had a lower risk of influenza (1.9%) than placebo controls (13.6%). Adverse events were similar in the two groups.Background Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications.The postexposure prophylactic efficacy of baloxavir in the household setting is unclear. Methods We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan.The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed. Results A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P