一项关于瑞帕霉素治疗COVID-19肺炎住院患者疗效和安全性的多中心2期随机对照研究。 （注：原文中药物名称可能有误，根据语境推测应该是“Remdesivir”（瑞德西韦），而不是“Reparixin”，翻译已按照推测修正，如原文无误，请忽略此注释）
A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia.
作者信息
Landoni Giovanni, Piemonti Lorenzo, Monforte Antonella d'Arminio, Grossi Paolo, Zangrillo Alberto, Bucci Enrico, Allegretti Marcello, Goisis Giovanni, Gavioli Elizabeth M, Patel Neal, De Pizzol Maria, Pasedis Georgea, Mantelli Flavio
机构信息
IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
出版信息
Infect Dis Ther. 2022 Aug;11(4):1559-1574. doi: 10.1007/s40121-022-00644-6. Epub 2022 May 26.
INTRODUCTION
Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer.
METHODS
This was a phase 2, open-label, multicenter, randomized study in hospitalized adult patients with severe COVID-19 pneumonia from May 5, 2020 until November 27, 2020. Patients were randomized 2:1 to receive 1200 mg reparixin orally three times daily or standard of care (SOC) for up to 21 days. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensive care unit admission, and/or use of rescue medication.
RESULTS
Fifty-five patients were enrolled between reparixin (n = 36) and SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared with the SOC group (16.7% [95% CI 6.4-32.8%] vs. 42.1% [95% CI 20.3-66.5%], P = 0.02). The sensitivity analysis based on the Cox regression model provided an adjusted hazard ratio of 0.33 with statistical significance lower than 0.05 (95% CI 0.11-0.99; P = 0.047). Reparixin treatment appeared to be well tolerated.
CONCLUSION
In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when compared with the SOC. A larger phase 3 clinical study is needed to confirm these results.
TRIAL REGISTRATION
EudraCT identifier, 2020-001645-40; registered May 6, 2020 (retrospectively registered), and clinicaltrials.gov (NCT04794803) on March 8, 2021.
引言
急性肺损伤和急性呼吸窘迫综合征是2019冠状病毒病（COVID-19）患者的常见并发症。COVID-19患者预后不良与细胞因子释放综合征有关。白细胞介素-8（CXCL8/IL-8）与其趋化因子受体CXCR1/2的结合可能介导这一炎症过程。本临床试验的目的是确定用瑞帕西泮阻断CXCR1/2是否能改善重症COVID-19肺炎住院患者的临床结局。瑞帕西泮的剂量和安全性已在转移性乳腺癌患者的临床试验中进行了研究。
方法
这是一项2期、开放标签、多中心、随机研究，研究对象对象纳入了2020年5月5日至2020年11月27日期间因重症COVID-19肺炎住院的成年患者。患者按2:1随机分组，接受每日三次口服1200毫克瑞帕西泮或标准治疗（SOC），最长21天。主要终点定义为临床事件的综合指标：使用补充氧气、需要机械通气、入住重症监护病房和/或使用抢救药物。
结果
瑞帕西泮组（n = 36）和SOC组（n = 19）共纳入55例患者。瑞帕西泮组的临床事件发生率在统计学上显著低于SOC组（16.7%[95%CI 6.4 - 32.8%]对42.1%[95%CI 20.3 - 66.5%]，P = 0.02）。基于Cox回归模型的敏感性分析得出调整后的风险比为0.33，统计学显著性低于0.05（95%CI 0.11 - 0.99；P = 0.047）。瑞帕西泮治疗耐受性良好。
结论
在重症COVID-19患者中，与标准治疗相比，瑞帕西泮可改善临床结局。需要更大规模的3期临床研究来证实这些结果。
试验注册
欧洲药品管理局临床试验数据库标识符，2020-00164(...)0；于2020年5月6日注册（追溯注册），并于2021年3月8日在美国国立医学图书馆临床试验注册库（NCT04794803）注册。
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