现在的位置: 首页时讯速递, 进展交流>正文
[Lancet Respir Med在线发表]:静脉扎那米韦与口服奥司他韦对流感住院患者疗效相似
2017年02月28日 时讯速递, 进展交流 暂无评论

Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial

Francisco M Marty, Joan Vidal-Puigserver, Carol Clark, et al

Lancet Respir Med

Published: 13 January 2017

DOI: http://dx.doi.org/10.1016/S2213-2600(16)30435-0

Background 背景

Neuraminidase inhibitors are effective for the treatment of acute uncomplicated influenza. However, there is an unmet need for intravenous treatment for patients admitted to hospital with severe influenza. We studied whether intravenous zanamivir was a suitable treatment in this setting.

神经氨酸酶抑制剂能够有效治疗急性非复杂性流感。然而,因严重流感住院的患者需要使用静脉药物治疗。我们对于静脉扎那米韦在这种情况下是否为适宜治疗进行了研究。

Methods 方法

In this international, randomised, double-blind, double-dummy, phase 3 trial, we recruited patients aged 16 years or older with severe influenza admitted to 97 hospitals from 26 countries. We randomly assigned patients (1:1:1 stratified by symptom onset ≤4 days or 5–6 days) to receive 300 mg or 600 mg intravenous zanamivir, or standard-of-care (75 mg oral oseltamivir) twice a day for 5–10 days; patients were followed up for 28 days. The randomisation schedule, including stratification, was generated using GlaxoSmithKline's RandAll software. Patients, site study staff, and sponsor were masked to study treatment. The primary endpoint was time to clinical response—a composite of vital sign stabilisation and hospital discharge—in the influenza-positive population. The trial was powered to show an improvement of 1·5 days or greater with 600 mg intravenous zanamivir. Pharmacokinetic, safety, and virology endpoints were also assessed. This trial is registered with ClinicalTrials.gov, number NCT01231620.

在这项国际随机双盲双模拟3期临床试验中,我们入选了26个国家97家医院收治的16岁以上重症流感患者。我们将患者随机分组(根据症状出现≤4 天或5–6 天按照1:1:1分层),接受300 mg或600 mg静脉扎那米韦,或标准治疗(口服奥司他韦75 mg),每日两次,疗程5-10天;患者接受28天的随访。随机分组包括分层均采用GlaxoSmithKline的RandAll软件进行。研究治疗分组对患者、研究中心人员及资助方隐藏。主要终点为流感阳性人群临床治疗反应所需时间(生命体征稳定及出院的综合指标)。试验样本量足以显示600 mg静脉扎那米韦组改善1.5天或更多。我们也评估了药代动力学、安全性及病毒学终点。试验在ClinicalTrials.gov网站注册,注册号NCT01231620。

Findings 结果

Between Jan 15, 2011, and Feb 12, 2015, 626 patients were randomly assigned to receive 300 mg intravenous zanamivir (n=201), 600 mg intravenous zanamivir (n=209), or 75 mg oral oseltamivir (n=205) twice a day; 11 patients discontinued the study before receiving any study treatment. 488 (78%) of 626 patients had laboratory-confirmed influenza. Compared with a median time to clinical response of 5·14 days in the 600 mg intravenous zanamivir group, the median time to clinical response was 5·87 days (difference of −0·73 days, 95% CI −1·79 to 0·75; p=0·25) in the 300 mg intravenous zanamivir group and 5·63 days (difference of −0·48 days, 95% CI −2·11 to 0·97; p=0·39) in the oseltamivir group. Four patients with influenza A/H1N1pdm09 in the oseltamivir group developed H275Y resistance mutations. Adverse events were reported in 373 (61%) of treated patients and were similar across treatment groups; the most common adverse events (300 mg intravenous zanamivir, 600 mg intravenous zanamivir, oseltamivir) were diarrhoea (10 [5%], 15 [7%], 14 [7%]), respiratory failure (11 [5%], 14 [7%], 11 [5%]), and constipation (7 [3%], 13 [6%], 10 [5%]). 41 (7%) treated patients died during the study (15 [7%], 15 [7%], 11 [5%]); the most common causes of death were respiratory failure and septic shock.

2011年1月15日至2015年2月12日期间,共有626名患者随机接受300 mg静脉扎那米韦(n = 201),600 mg静脉扎那米韦(n = 209),或75 mg口服奥司他韦(n = 205)每日两次;11例患者在接受研究药物前终止研究。626名患者中488名(78%)为实验室确诊的流感患者。600 mg静脉扎那米韦组临床治疗反应中位时间为5.14天,与此相比,300 mg静脉扎那米韦组为5·87 天(差异-0·73 天,95% CI -1·79 to 0·75; p=0·25),奥司他韦组为5·63 天(差异 -0·48天,95% CI −2·11 to 0·97; p=0·39)。奥司他韦组4名甲型流感H1N1pdm09患者发生H275Y耐药突变。共有373名患者(61%)报告不良事件,不同治疗组比例相似;最常见的不良事件(300 mg静脉扎那米韦,600 mg静脉扎那米韦,奥司他韦)为腹泻 (10 [5%], 15 [7%], 14 [7%]),呼吸功能衰竭 (11 [5%], 14 [7%], 11 [5%]), 及便秘 (7 [3%], 13 [6%], 10 [5%])。接受治疗患者中41名(7%)在治疗期间死亡(15 [7%], 15 [7%], 11 [5%]);最常见死因为呼吸功能衰竭和感染性休克。

Interpretation 结论

Time to clinical response to intravenous zanamivir dosed at 600 mg was not superior to oseltamivir or 300 mg intravenous zanamivir. All treatments had a similar safety profile in hospitalised patients with severe influenza.

600 mg静脉扎那米韦治疗临床反应时间并不优于奥司他韦或300 mg静脉扎那米韦。对于重症流感住院患者,所有治疗的安全性相似。

Funding

GlaxoSmithKline.

给我留言

您必须 [ 登录 ] 才能发表留言!

×
腾讯微博