From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Groton, CT (R.J.F., H.S.); Global Product Development, Pfizer International Organization, Paris (G.L.); Pfizer, Chicago (A.M.B.); Global Product Development, Pfizer, Lake Forest, IL (W.Z., W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Medical and Safety, Pfizer Research and Development UK, Sandwich, United Kingdom (V.M.H.); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Global Product Development, Pfizer, New York (R.P.).
N Engl J Med. 2024 Jul 18;391(3):224-234. doi: 10.1056/NEJMoa2309002.
Clinical trials of treatments for coronavirus disease 2019 (Covid-19) have not shown a significant benefit of postexposure prophylaxis.
We conducted a phase 2-3 double-blind trial to assess the efficacy and safety of nirmatrelvir-ritonavir in asymptomatic, rapid antigen test-negative adults who had been exposed to a household contact with Covid-19 within 96 hours before randomization. The participants were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir-ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) every 12 hours for 5 days or for 10 days or matching placebo for 5 or 10 days. The primary end point was the development of symptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, confirmed on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) or rapid antigen testing, through 14 days in participants who had a negative RT-PCR test at baseline.
A total of 2736 participants were randomly assigned to a trial group - 921 to the 5-day nirmatrelvir-ritonavir group, 917 to the 10-day nirmatrelvir-ritonavir group, and 898 to the placebo group. Symptomatic, confirmed SARS-CoV-2 infection developed by day 14 in 2.6% of the participants in the 5-day nirmatrelvir-ritonavir group, 2.4% of those in the 10-day nirmatrelvir-ritonavir group, and 3.9% of those in the placebo group. In each nirmatrelvir-ritonavir group, the percentage of participants in whom symptomatic, confirmed SARS-CoV-2 infection developed did not differ significantly from that in the placebo group, with risk reductions relative to placebo of 29.8% (95% confidence interval [CI], -16.7 to 57.8; P = 0.17) in the 5-day nirmatrelvir-ritonavir group and 35.5% (95% CI, -11.5 to 62.7; P = 0.12) in the 10-day nirmatrelvir-ritonavir group. The incidence of adverse events was similar across the trial groups, with dysgeusia being the most frequently reported adverse event (in 5.9% and 6.8% of the participants in the 5-day and 10-day nirmatrelvir-ritonavir groups, respectively, and in 0.7% of those in the placebo group).
In this placebo-controlled trial, postexposure prophylaxis with nirmatrelvir-ritonavir for 5 or 10 days did not significantly reduce the risk of symptomatic SARS-CoV-2 infection. (Funded by Pfizer; ClinicalTrials.gov number, NCT05047601.).
针对 2019 年冠状病毒病（COVID-19）的治疗方法的临床试验并未显示出暴露后预防的显著益处。
我们进行了一项 2-3 期双盲试验，以评估奈玛特韦-利托那韦在无症状、快速抗原检测阴性的成年人中的疗效和安全性，这些成年人在随机分组前 96 小时内与 COVID-19 的家庭接触者接触。参与者以 1:1:1 的比例随机分配，接受奈玛特韦-利托那韦（奈玛特韦 300 毫克和利托那韦 100 毫克）每 12 小时一次，连续 5 天或 10 天，或在 5 天或 10 天内接受匹配的安慰剂。主要终点是通过 14 天的基线时 RT-PCR 检测为阴性的参与者中出现有症状的 SARS-CoV-2（严重急性呼吸综合征冠状病毒 2）感染，通过 RT-PCR 或快速抗原检测确认。
共有 2736 名参与者被随机分配到一个试验组 - 921 名参与者接受 5 天的奈玛特韦-利托那韦组，917 名参与者接受 10 天的奈玛特韦-利托那韦组，898 名参与者接受安慰剂组。在奈玛特韦-利托那韦组中，5 天组中有 2.6%的参与者、10 天组中有 2.4%的参与者、安慰剂组中有 3.9%的参与者在第 14 天出现有症状的、经确认的 SARS-CoV-2 感染。在每个奈玛特韦-利托那韦组中，与安慰剂组相比，有症状的、经确认的 SARS-CoV-2 感染发展的参与者比例没有显著差异，5 天奈玛特韦-利托那韦组的风险降低了 29.8%（95%置信区间[CI]，-16.7 至 57.8；P=0.17），10 天奈玛特韦-利托那韦组的风险降低了 35.5%（95%CI，-11.5 至 62.7；P=0.12）。试验组之间不良反应的发生率相似，味觉障碍是最常报告的不良反应（分别在 5 天和 10 天的奈玛特韦-利托那韦组中，有 5.9%和 6.8%的参与者，而在安慰剂组中为 0.7%）。
在这项安慰剂对照试验中，奈玛特韦-利托那韦暴露后预防 5 天或 10 天并未显著降低有症状的 SARS-CoV-2 感染风险。（由辉瑞公司资助；临床试验.gov 编号，NCT05047601。）
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