Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.
Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.
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DOI：
10.1164/rccm.202112-2836oc
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发表时间：
2022-09-15
影响因子：
24.7
通讯作者：
Ginde, Adit A.
中科院分区：
文献类型：
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作者：
Douin, David J.;Siegel, Lianne;Grandits, Greg;Phillips, Andrew;Aggarwal, Neil R.;Baker, Jason;Brown, Samuel M.;Chang, Christina C.;Goodman, Anna L.;Grund, Birgit;Higgs, Elizabeth S.;Hough, Catherine L.;Murray, Daniel D.;Paredes, Roger;Parmar, Mahesh;Pett, Sarah;Polizzotto, Mark N.;Sandkovsky, Uriel;Self, Wesley H.;Young, Barnaby E.;Babiker, Abdel G.;Davey, Victoria J.;Kan, Virginia;Gelijns, Annetine C.;Matthews, Gail;Thompson, B. Taylor;Lane, H. Clifford;Neaton, James D.;Lundgren, Jens D.;Ginde, Adit A.
有关冠状病毒病(新冠肺炎)自然病史的不确定性导致治疗试验的疗效终点选择困难。捕捉出院后发生的结果可能会改善新冠肺炎住院患者的临床恢复评估。评估新冠肺炎患者住院90天的临床病程，比较三种不同的康复定义。我们使用来自三个中和单抗临床试验的汇集数据来比较：1)医院出院方法；2)新冠肺炎住院患者治疗试验持续恢复方法；以及3)综合方法。在登记时，所有患者都是在非ICU环境中住院，没有器官衰竭或新冠肺炎的主要肺外表现。我们将不和谐定义为恢复时间之间的差异。在850名登记的参与者中，170人(20%)的出院情况与综合治疗方法不一致，其中包括126人再次住院，24人在初次出院后死亡。不和谐的参与者年龄更大(中位年龄，68岁比59岁；P <； 0.001)，并且更多的人有共病(84%比70%；P <； 0.001)。在170名不和谐的参与者中，106人(62%)的出院后事件被TICO方法捕捉到。在使用新冠肺炎入院的患者中，20%的患者在随机分组后90天内发生了临床上显著的出院后事件，这些患者使用医院出院的方法被认为是“康复”的。使用TICO方法在后续行动的时间长短与实际限制之间取得平衡。然而，新冠肺炎疗法的临床试验应该使用长达90天的随访时间，以更准确地评估临床恢复情况。
Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P < 0.001) and more had a comorbidity (84% vs. 70%; P < 0.001). Of 170 discordant participants, 106 (62%) had postdischarge events captured by the TICO approach. Among patients hospitalized with COVID-19, 20% had clinically significant postdischarge events within 90 days after randomization in patients who would be considered “recovered” using the hospital discharge approach. Using the TICO approach balances length of follow-up with practical limitations. However, clinical trials of COVID-19 therapeutics should use follow-up times up to 90 days to assess clinical recovery more accurately.