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 ≥50 years) and vaccination status (yes 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

中文翻译：

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Molnupiravir 加常规护理与单独常规护理作为不良结果风险增加的 COVID-19 成人早期治疗的比较 (PANORAMIC)：一项开放标签、平台适应性随机对照试验

molnupiravir（一种针对 SARS-CoV-2 的口服抗病毒药物）的安全性、有效性和成本效益尚未在社区中因 COVID-19 发病和死亡风险增加的已接种疫苗的患者中得到证实。我们的目的是确定在常规护理中添加莫努匹拉韦是否会减少该人群中与 COVID-19 相关的住院率和死亡人数。PANORAMIC 是一项总部位于英国的全国性多中心、开放标签、多组、前瞻性、平台适应性随机对照试验。符合资格的参与者年龄为 50 岁或以上，或者年龄为 18 岁或以上，患有相关合并症，并且在社区内因确诊的 COVID-19 感到不适的时间不超过 5 天。参与者被随机分配 (1:1) 接受 800 mg molnupiravir，每天两次，持续 5 天，加常规护理或仅常规护理。使用安全的基于网络的系统（Spinnaker）进行随机分组，按年龄（<50 岁≥50 岁）和疫苗接种状况（是否）进行分层。随机分组后 28 天，通过自行填写的在线每日日记追踪 COVID-19 的结果。主要结局是随机分组后 28 天内全因住院或死亡，这是使用贝叶斯模型对所有随机分组的合格参与者进行分析。该试验已在 ISRCTN 注册，编号为 30448031。2021 年 12 月 8 日至 2022 年 4 月 27 日期间，26 411 名参与者被随机分配，其中 12 821 名参与者接受莫努匹拉韦加常规治疗，12 962 名参与者接受单独常规治疗，628 名参与者分配到其他治疗组（将单独报告）。主要分析人群包括来自莫努匹拉韦加常规护理组的 12 529 名参与者和来自常规护理组的 12 525 名参与者。人群的平均年龄为 56·6 岁 (SD 12·6)，25 708 名参与者中的 24 290 人 (94%) 至少接种了三剂 SARS-CoV-2 疫苗。莫努匹拉韦加常规护理组的 12 529 名参与者中有 105 名 (1%) 住院或死亡，而常规护理组 12 525 名参与者中有 98 名 (1%) 住院或死亡（调整比值比 1·06 [95% 贝叶斯可信区间 0] ·81–1·41]；优势概率0·33)。没有证据表明亚组之间存在治疗相互作用。莫努匹拉韦加常规护理组的 12 774 名参与者中有 50 名 (0·4%) 记录了严重不良事件，常规护理组的 12 934 名参与者中有 45 名 (0·3%) 记录了严重不良事件。这些事件均未被判定与莫努匹拉韦有关。Molnupiravir 并未降低社区中已接种疫苗的高危成年人中与 COVID-19 相关的住院或死亡频率。英国国家健康与护理研究所