Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial.
Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial.
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DOI：
10.1016/s0140-6736(22)02597-1
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发表时间：
2023-01-28
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莫努匹拉韦是一种针对SARS-CoV-2的口服抗病毒药物，其安全性、有效性和成本效益尚未在社区接种疫苗的患者中得到确定，这些患者的COVID-19发病率和死亡率风险增加。我们的目的是确定在常规治疗中添加莫努匹拉韦是否减少了该人群中与COVID-19相关的住院和死亡人数。PANORAMIC是一项基于英国的、国家、多中心、开放标签、多组、前瞻性、平台适应性随机对照试验。符合条件的参与者年龄在50岁或以上-或年龄在18岁或以上并患有相关合并症-并且在社区中因确诊的COVID-19而不适5天或更少。参与者被随机分配（1：1）接受800 mg molnupiravir，每天两次，持续5天，加上常规护理或仅常规护理。使用安全的基于网络的系统（Spinnaker）进行随机化，并按年龄（<50岁vs ≥50岁）和疫苗接种状态（是vs否）分层。在随机化后28天内，通过自我完成的在线日记跟踪COVID-19结局。主要结局是随机化后28天内的全因住院或死亡，在所有随机分配的合格参与者中使用贝叶斯模型进行分析。本试验已在ISRCTN注册，编号30448031。在2021年12月8日至2022年4月27日期间，26411名参与者被随机分配，其中12821人接受莫努匹拉韦加常规治疗，12962人接受常规治疗，628人接受其他治疗组（将单独报告）。来自莫努匹拉韦加常规护理组的12529名参与者和来自常规护理组的12525名参与者被纳入主要分析人群。人群的平均年龄为56.6岁（SD 12.6），25708名参与者中有24290人（94%）至少接种了三剂SARS-CoV-2疫苗。莫努匹拉韦加常规治疗组12529例受试者中有105例（1%）记录了住院或死亡，而常规治疗组12525例受试者中有98例（1%）记录了住院或死亡（调整后的比值比为1.06 [95%贝叶斯可信区间为0.81 - 1.41];优效概率为0.33）。没有证据表明亚组之间存在治疗相互作用。在莫努匹拉韦加常规治疗组的12774名参与者中，有50名（0.4%）记录了严重不良事件，在常规治疗组的12934名参与者中，有45名（0.3%）记录了严重不良事件。这些事件均被判定为与莫努匹韦无关。莫努匹拉韦并没有降低社区中高风险接种疫苗的成年人的COVID-19相关住院或死亡频率。英国国家健康与护理研究所
The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. UK National Institute for Health and Care Research