Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
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DOI：
10.1186/s13054-020-03117-9
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发表时间：
2020-07-11
期刊：
影响因子：
15.1
通讯作者：
Dres, Martin
中科院分区：
文献类型：
--
作者：
Lecronier, Marie;Beurton, Alexandra;Dres, Martin
研究背景严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）疫情正在全球范围内蔓延。到目前为止，还没有具体的治疗方法令人信服地证明其疗效。羟氯喹和洛匹那韦/利托那韦有潜在的利益，但病毒学和临床数据是稀缺的，特别是在危重患者。MethodsThe本报告的机会，同情使用和连续的药物短缺比较两种治疗方案，洛匹那韦/利托那韦和羟氯喹的效果，相比标准的护理。主要结局为第1天至第28天的治疗升级（插管、皮质外膜氧合支持或肾脏替代治疗）。次要结局包括第28天无呼吸机天数、第14天和第28天死亡率、治疗安全性问题和呼吸道变化以及血浆病毒载量结果80例患者在4周内接受治疗，并纳入分析：22例（28%）患者仅接受标准治疗，20例（25%）患者接受洛匹那韦/利托那韦联合标准治疗，38例（47%）患者接受羟氯喹和标准治疗。3组之间的基线特征平衡良好。分别有9例（41%）、10例（50%）和15例（39%）接受标准治疗、标准治疗+洛匹那韦/利托那韦、标准治疗+羟氯喹的患者发生治疗递增（p=0.567）。两组在第28天无呼吸机天数以及第14天和第28天死亡率方面无显著差异。最后，两组患者的病毒呼吸或血浆载量在入院至第7天之间没有显著变化。结论在因SARS-CoV-2相关肺炎入院的危重患者中，与标准治疗相比，羟氯喹或洛匹那韦/利托那韦治疗仅在第28天需要治疗升级的患者比例方面没有差异。需要进一步的随机对照试验来证明这些药物在这种情况下是否有用。
BackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.MethodsThe present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.ResultsEighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p=0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7.ConclusionIn critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.