Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
J Infect Dis. 2023 Aug 31;228(Suppl 2):S83-S91. doi: 10.1093/infdis/jiad300.
Time to symptom resolution measures were used in outpatient coronavirus disease 2019 (COVID-19) treatment trials without prior validation.
ACTIV-2/A5401 trial participants completed a COVID-19 diary assessing 13 targeted symptoms and global experience (overall COVID-19 symptoms, return to pre-COVID-19 health) daily for 29 days. We evaluated concordance of time to sustained (2 days) resolution of all targeted symptoms (TSR) with resolution of overall symptoms and return to health in participants receiving placebo.
The analysis included 77 high-risk and 81 standard-risk participants with overall median 6 days of symptoms at entry and median age 47 years, 50% female, 82% white, and 31% Hispanic/Latino. Correlation between TSR and resolution of overall symptoms was 0.80 and 0.68, and TSR and return to health, 0.66 and 0.57 for high- and standard-risk groups, respectively. Of the high- and standard-risk participants, 61% and 79%, respectively, achieved targeted symptom resolution, of which 47% and 43%, respectively, reported symptom recurrence. Requiring >2 days to define sustained resolution reduced the frequency of recurrences.
There was good internal consistency between TSR and COVID-19-specific global outcomes, supporting TSR as a trial end point. Requiring >2 days of symptom resolution better addresses natural symptom fluctuations but must be balanced against the potential influence of non-COVID-19 symptoms.
NCT04518410.
在没有事先验证的情况下，时间到症状缓解措施被用于门诊 2019 冠状病毒病（COVID-19）治疗试验。
ACTIV-2/A5401 试验参与者每天填写一份 COVID-19 日记，评估 13 项靶向症状和总体体验（总体 COVID-19 症状、恢复到 COVID-19 前的健康状态），共 29 天。我们评估了在接受安慰剂的参与者中，所有靶向症状（TSR）持续缓解（2 天）与总体症状缓解和恢复健康的一致性。
分析包括 77 名高风险和 81 名标准风险参与者，总体中位数为 6 天的症状进入期，中位数年龄为 47 岁，50%为女性，82%为白人，31%为西班牙裔/拉丁裔。TSR 与总体症状缓解的相关性分别为 0.80 和 0.68，与恢复健康的相关性分别为 0.66 和 0.57，分别用于高风险和标准风险组。高风险和标准风险参与者中，分别有 61%和 79%达到了靶向症状缓解，其中分别有 47%和 43%报告了症状复发。要求>2 天才能定义持续缓解会降低复发的频率。
TSR 与 COVID-19 特定的总体结局之间存在良好的内部一致性，支持 TSR 作为试验终点。要求>2 天的症状缓解更好地解决了自然症状波动问题，但必须与非 COVID-19 症状的潜在影响相平衡。
NCT04518410。
