Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities A Randomized Clinical Trial
Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities A Randomized Clinical Trial
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DOI：
10.1001/jama.2021.88282021
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发表时间：
2021-06-03
影响因子：
120.7
通讯作者：
Skovronsky, Daniel M.
中科院分区：
文献类型：
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作者：
Cohen, Myron S.;Nirula, Ajay;Skovronsky, Daniel M.
重要性需要采取预防性干预措施，以保护熟练护理和辅助生活设施的居民和工作人员在其设施爆发期间免受COVID-19的影响。Bamlanivimab是一种针对SARS-CoV-2的中和性单克隆抗体，可能会对SARS-CoV-2感染和COVID-19产生快速保护作用。目的确定bamlanivimab对居民以及熟练护理和辅助生活机构工作人员中COVID-19发病率的影响。设计、设置和参与者：随机、双盲、单剂量、3期试验，招募了美国74家专业护理和辅助生活机构的居民和工作人员，至少有1例确诊的SARS-CoV-2索引病例。2020年8月2日至11月20日，共有1175名参与者参加了研究。数据库锁定于2021年1月13日触发，当时所有参与者均达到研究第57天。参与者随机接受单次静脉输注bamlanivimab，4200 mg（n = 588）或安慰剂（n = 587）。主要结局和指标主要结局是COVID-19的发生率，定义为通过逆转录酶-聚合酶链反应检测到SARS-CoV-2，并且在检测后21天内，在随机分组后8周内，疾病严重程度为轻度或更严重。关键次要结局包括中度或重度COVID-19的发生率和SARS-CoV-2感染的发生率。结果预防人群共包括966名参与者（666名工作人员和300名居民），他们在基线时SARS-CoV-2感染和血清学均为阴性（平均年龄53.0 [范围，18-104]岁; 722名[74.7%]女性）。与安慰剂相比，Bamlanivimab显著降低了预防人群中COVID-19的发病率（8.5% vs 15.2%;比值比，0.43 [95%CI，0.28-0.68]; P <0.001;绝对风险差，-6.6 [95%CI，-10.7至-2.6]个百分点）。截至第57天，报告了5例归因于COVID-19的死亡;均发生在安慰剂组。在接受研究产品的1175名参与者（安全性人群）中，bamlanivimab组发生不良事件的参与者比例为20.1%，安慰剂组为18.9%。最常见的不良事件是尿路感染（12名接受bamlanivimab的参与者[2%]和14名接受安慰剂的参与者[2.4%]）和高血压（7名接受bamlanivimab的参与者[1.2%]和10名接受安慰剂的参与者[1.7%]）。结论和相关性在熟练护理和辅助生活设施的居民和工作人员中，2020年8月至11月期间使用bamlanivimab单药治疗降低了COVID-19感染的发生率。需要进一步的研究来评估目前的病毒株模式与单克隆抗体联合治疗的预防效果。这项随机临床试验评估了单次静脉输注bamlanivimab与安慰剂对居民和专业护理和辅助生活设施工作人员中COVID-19发病率的影响。问题在SARS-CoV高风险的居民和专业护理和辅助生活设施工作人员中，2暴露，bamlanivimab对COVID-19的发病率有什么影响？这项随机的3期临床试验包括966名参与者，他们是美国专业护理和辅助生活设施的居民和工作人员，至少有1例确诊的SARS-CoV-2指数病例，并且在基线时SARS-CoV-2感染和血清学呈阴性，于2020年8月至11月入组。接受bamlanivimab治疗与安慰剂治疗的患者中，COVID-19感染的发生率分别为8.5%和15.2%，差异具有统计学意义。这意味着与安慰剂相比，Bamlanivimab单药治疗降低了熟练护理和辅助生活设施的居民和工作人员患COVID-19的风险。
Importance Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. Objective To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. Design, Setting, and Participants Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. Interventions Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200 mg (n = 588), or placebo (n = 587). Main Outcomes and Measures The primary outcome was incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. Results The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5% vs 15.2%; odds ratio, 0.43 [95% CI, 0.28-0.68]; P < .001; absolute risk difference, -6.6 [95% CI, -10.7 to -2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). Conclusions and Relevance Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy.This randomized clinical trial assesses the effect of a single intravenous infusion of bamlanivimab vs placebo on incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities.Question Among residents and staff of skilled nursing and assisted living facilities with high risk of SARS-CoV-2 exposure, what is the effect of bamlanivimab on the incidence of COVID-19? Findings This randomized phase 3 clinical trial included 966 participants who were residents and staff at US skilled nursing and assisted living facilities with at least 1 confirmed SARS-CoV-2 index case and who were negative at baseline for SARS-CoV-2 infection and serology, enrolled from August to November 2020. The incidence of COVID-19 infection among those treated with bamlanivimab vs placebo was 8.5% vs 15.2%, respectively, a difference that was statistically significant. Meaning Bamlanivimab monotherapy compared with placebo reduced the risk of COVID-19 in residents and staff of skilled nursing and assisted living facilities.