Federal State Budgetary Institution Central Clinical Hospital of the Management Affair of President Russian Federation (FSBI CCH), Moscow, Russian Federation.
Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University of the Ministry of Healthcare of the Russian Federation" (FSBEI HE BSMU of the Ministry of Health of Russia), Ufa, Russian Federation.
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19.
The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia.
206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy.
The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders.
63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups.
In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate.
The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).
这项双盲、安慰剂对照、III 期 CORONA 临床试验的目的是评估白细胞介素 6 受体抑制剂利维利单抗（LVL）在重症 COVID-19 患者中的疗效和安全性。
该研究纳入了 217 名患者。合格受试者为年龄 18 岁或以上的男性和非孕妇，因严重 COVID-19 肺炎住院。
206 名受试者按 1:1 比例随机（随机）接受 LVL 324mg 或安慰剂单次皮下给药，均联合标准治疗（SOC）。204 名患者接受了分配的治疗。在 LVL/安慰剂给药后，如果症状恶化，研究者可以进行单次开放标签 LVL 324mg 给药作为抢救治疗。
主要疗效终点是第 14 天 7 级有序量表上持续临床改善的患者比例。抢救治疗后获得的所有疗效数据均视为缺失。对于主要疗效分析，所有缺失数据的受试者均视为无应答者。
LVL 组和安慰剂组分别有 63.1%和 42.7%的患者在第 14 天达到持续临床改善（P = .0017）。两组药物不良反应的频率相似。
在需要或不需要氧气治疗（但没有其他活动性感染迹象）且影像学证实为 SARS-CoV-2 肺炎的患者中，LVL+SOC 的给药可提高持续临床改善率。
该试验在美国国立卫生研究院（ClinicalTrials.gov；NCT04397562）注册。
