Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
Division of Medical Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
Front Immunol. 2023 Oct 27;14:1255292. doi: 10.3389/fimmu.2023.1255292. eCollection 2023.
Conestat alfa (ConA), a recombinant human C1 inhibitor, may prevent thromboinflammation.
We conducted a randomized, open-label, multi-national clinical trial in which hospitalized adults at risk for progression to severe COVID-19 were assigned in a 2:1 ratio to receive either 3 days of ConA plus standard of care (SOC) or SOC alone. Primary and secondary endpoints were day 7 disease severity on the WHO Ordinal Scale, time to clinical improvement within 14 days, and safety, respectively.
The trial was prematurely terminated because of futility after randomization of 84 patients, 56 in the ConA and 28 in the control arm. At baseline, higher WHO Ordinal Scale scores were more frequently observed in the ConA than in the control arm. On day 7, no relevant differences in the primary outcome were noted between the two arms ( = 0.11). The median time to defervescence was 3 days, and the median time to clinical improvement was 7 days in both arms ( = 0.22 and 0.56, respectively). Activation of plasma cascades and endothelial cells over time was similar in both groups. The incidence of adverse events (AEs) was higher in the intervention arm (any AE, 30% with ConA vs. 19% with SOC alone; serious AE, 27% vs. 15%; death, 11% vs. 0%). None of these were judged as being related to the study drug.
The study results do not support the use of ConA to prevent COVID-19 progression.
https://clinicaltrials.gov, identifier NCT04414631.
康奈司他（ConA），一种重组人 C1 抑制剂，可能预防血栓炎症。
我们进行了一项随机、开放标签、多中心临床试验，将有进展为重症 COVID-19 风险的住院成人患者按 2:1 的比例随机分为 ConA 加标准治疗（SOC）组或 SOC 组。主要和次要终点分别为第 7 天 WHO 等级量表的疾病严重程度、14 天内临床改善的时间和安全性。
该试验因无效而提前终止，在随机分配了 84 名患者后，ConA 组 56 名，对照组 28 名。在基线时，ConA 组的 WHO 等级量表评分高于对照组。在第 7 天，两组间主要结局无显著差异（ = 0.11）。退热中位数时间为 3 天，临床改善中位数时间为 7 天，两组均为 7 天（ = 0.22 和 0.56）。两组的血浆级联和内皮细胞的激活随时间相似。干预组的不良事件（AE）发生率较高（任何 AE，ConA 组为 30%，SOC 组为 19%；严重 AE，ConA 组为 27%，SOC 组为 15%；死亡，ConA 组为 11%，SOC 组为 0%）。这些均未被判断与研究药物有关。
研究结果不支持使用 ConA 预防 COVID-19 进展。
[临床试验注册网址]，标识符 NCT04414631。
