From Global Product Development, Pfizer, Collegeville, PA (J.H.); Global Product Development, Pfizer, Groton, CT (R.J.F.); Global Product Development, Pfizer, Lake Mary (C.Y.), and Global Product Development, Pfizer, Tampa (J.M.R.) - both in Florida; Global Product Development, Pfizer, Lexington, KY (D.F.); Global Product Development, Pfizer, New York (M.A., W.B., R.P.); Global Product Development, Pfizer, Lake Forest, IL (W.W.); Early Clinical Development, Pfizer, Cambridge, MA (M.L.B.); Pfizer, Sandwich, United Kingdom (V.M.H.); the Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Haskovo, Bulgaria (V.K.); and Méchnikov Project, Köhler and Milstein Research, Anahuac-Mayab University, Mérida, Mexico (J.A.S.-C.).
N Engl J Med. 2024 Apr 4;390(13):1186-1195. doi: 10.1056/NEJMoa2309003.
Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established.
In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvir-ritonavir or placebo every 12 hours for 5 days. Patients who were fully vaccinated against Covid-19 and who had at least one risk factor for severe disease, as well as patients without such risk factors who had never been vaccinated against Covid-19 or had not been vaccinated within the previous year, were eligible for participation. Participants logged the presence and severity of prespecified Covid-19 signs and symptoms daily from day 1 through day 28. The primary end point was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Covid-19-related hospitalization and death from any cause were also assessed through day 28.
Among the 1296 participants who underwent randomization and were included in the full analysis population, 1288 received at least one dose of nirmatrelvir-ritonavir (654 participants) or placebo (634 participants) and had at least one postbaseline visit. The median time to sustained alleviation of all targeted signs and symptoms of Covid-19 was 12 days in the nirmatrelvir-ritonavir group and 13 days in the placebo group (P = 0.60). Five participants (0.8%) in the nirmatrelvir-ritonavir group and 10 (1.6%) in the placebo group were hospitalized for Covid-19 or died from any cause (difference, -0.8 percentage points; 95% confidence interval, -2.0 to 0.4). The percentages of participants with adverse events were similar in the two groups (25.8% with nirmatrelvir-ritonavir and 24.1% with placebo). In the nirmatrelvir-ritonavir group, the most commonly reported treatment-related adverse events were dysgeusia (in 5.8% of the participants) and diarrhea (in 2.1%).
The time to sustained alleviation of all signs and symptoms of Covid-19 did not differ significantly between participants who received nirmatrelvir-ritonavir and those who received placebo. (Supported by Pfizer; EPIC-SR ClinicalTrials.gov number, NCT05011513.).
奈玛特韦/利托那韦是一种用于治疗轻度至中度 2019 冠状病毒病（COVID-19）的抗病毒药物。该药在有发生重症 COVID-19 标准风险的患者或已完全接种疫苗且有至少 1 项发生重症 COVID-19 风险因素的患者中的疗效尚未确定。
在这项 2 期-3 期试验中，我们以 1:1 的比例随机分配在过去 5 天内出现症状且确诊 COVID-19 的成年人，每 12 小时接受奈玛特韦/利托那韦或安慰剂治疗，共 5 天。有 COVID-19 疫苗完全接种史且有发生重症疾病的至少 1 项风险因素的患者，以及无这些风险因素但从未接种过 COVID-19 疫苗或在过去 1 年内未接种过疫苗的患者，有资格参与。参与者从第 1 天至第 28 天每天记录特定的 COVID-19 症状和体征的出现和严重程度。主要终点是所有目标 COVID-19 症状和体征持续缓解的时间。COVID-19 相关住院和任何原因导致的死亡也在第 28 天进行评估。
在接受随机分组且纳入全分析人群的 1296 名参与者中，有 1288 名（654 名参与者接受奈玛特韦/利托那韦治疗，634 名参与者接受安慰剂治疗）至少接受了 1 次治疗并至少有 1 次基线后访视。奈玛特韦/利托那韦组和安慰剂组中所有目标 COVID-19 症状和体征持续缓解的中位时间分别为 12 天和 13 天（P=0.60）。奈玛特韦/利托那韦组有 5 名（0.8%）参与者因 COVID-19 住院，安慰剂组有 10 名（1.6%）参与者住院（差异，-0.8 个百分点；95%置信区间，-2.0 至 0.4）。两组的不良事件发生率相似（奈玛特韦/利托那韦组为 25.8%，安慰剂组为 24.1%）。在奈玛特韦/利托那韦组中，最常报告的与治疗相关的不良事件为味觉障碍（5.8%的参与者）和腹泻（2.1%）。
在接受奈玛特韦/利托那韦治疗的患者与接受安慰剂治疗的患者中，所有 COVID-19 症状和体征持续缓解的时间无显著差异。（由辉瑞公司资助；EPIC-SR 临床试验.gov 编号，NCT05011513。）
