扎那米韦预防健康成年人流感：一项随机对照试验。

Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial.

作者信息

Monto A S, Robinson D P, Herlocher M L, Hinson J M, Elliott M J, Crisp A

机构信息

School of Public Health, University of Michigan, Ann Arbor 48109-2029, USA.

出版信息

JAMA. 1999 Jul 7;282(1):31-5. doi: 10.1001/jama.282.1.31.

DOI:10.1001/jama.282.1.31

PMID:10404908

Abstract

CONTEXT

The neuraminidase inhibitor zanamivir, a sialic acid analog administered directly to the respiratory tract, has been demonstrated in clinical studies to be effective in treatment of type A and B influenza. It has also been shown to prevent influenza infection and disease in an experimental model.

OBJECTIVE

To examine the efficacy of zanamivir, administered once daily, in the prevention of influenza infection and disease.

DESIGN

Double-blind, randomized, placebo-controlled trial.

SETTING

Two midwestern university communities.

PARTICIPANTS

A total of 1107 healthy adults (mean age [range], 29 [18-69] years) were recruited in November 1997, before the influenza season.

INTERVENTION

At the start of the influenza outbreak, 554 subjects were randomized to receive placebo and 553 to receive zanamivir. The drug, 10 mg once per day, or identical placebo was administered by oral inhalation for a 4-week period.

MAIN OUTCOME MEASURES

Illness occurrence was recorded by participants daily and records were evaluated weekly. Specimens were collected for viral isolation when symptoms were reported within 3 days of illness onset. Infection was also identified by testing paired serum samples for rise in antibody titer against the circulating influenza viruses.

RESULTS

Zanamivir was 67% efficacious (95% confidence interval [CI], 39%-83%; P<.001) in preventing laboratory-confirmed clinical influenza meeting the case definition and 84% efficacious (95% CI, 55%-94%; P=.001) in preventing laboratory-confirmed illnesses with fever. All influenza infections occurring during the season, with or without symptoms, were prevented with an efficacy of 31% (95% CI, 4%-50%; P=.03). The nature and incidence of adverse events in the zanamivir group did not differ from placebo. Compliance with the once-daily dosage was high.

CONCLUSIONS

Zanamivir administered once daily is efficacious and well tolerated in the prevention of influenza for a 4-week period in healthy adults.

摘要

背景

神经氨酸酶抑制剂扎那米韦是一种直接作用于呼吸道的唾液酸类似物，临床研究已证实其对甲型和乙型流感的治疗有效。在实验模型中也显示其能预防流感感染和疾病。

目的

研究每日服用一次扎那米韦预防流感感染和疾病的疗效。

设计

双盲、随机、安慰剂对照试验。

地点

两个中西部大学社区。

参与者

1997年11月流感季节开始前，共招募了1107名健康成年人（平均年龄[范围]，29[18 - 69]岁）。

干预措施

在流感爆发开始时，554名受试者随机接受安慰剂，553名接受扎那米韦。药物（10毫克，每日一次）或相同的安慰剂通过口服吸入给药，为期4周。

主要观察指标

参与者每天记录发病情况，每周评估记录。在发病后3天内出现症状时采集标本进行病毒分离。还通过检测配对血清样本中针对流行流感病毒的抗体滴度升高来确定感染情况。

结果

扎那米韦在预防符合病例定义的实验室确诊临床流感方面有效率为67%（95%置信区间[CI]，39% - 83%；P <.001），在预防实验室确诊的发热疾病方面有效率为84%（95%CI，55% - 94%；P =.001）。该季节发生的所有流感感染，无论有无症状，预防有效率为31%（95%CI，4% - 50%；P =.03）。扎那米韦组不良事件的性质和发生率与安慰剂组无差异。每日一次剂量的依从性很高。