An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19.
An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19.
复制标题
一项针对Lopinavir/Ritonavir，Lopinavir/Ritonavir Plus IFN-β-1A和羟基氯喹对Covid-19患者的开放标签随机对照试验。
DOI：
10.1016/j.cmi.2021.05.020
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
DisCoVeRy study group
中科院分区：
文献类型：
--
作者：
Ader F;Peiffer-Smadja N;Poissy J;Bouscambert-Duchamp M;Belhadi D;Diallo A;Delmas C;Saillard J;Dechanet A;Mercier N;Dupont A;Alfaiate T;Lescure FX;Raffi F;Goehringer F;Kimmoun A;Jaureguiberry S;Reignier J;Nseir S;Danion F;Clere-Jehl R;Bouiller K;Navellou JC;Tolsma V;Cabié A;Dubost C;Courjon J;Leroy S;Mootien J;Gaci R;Mourvillier B;Faure E;Pourcher V;Gallien S;Launay O;Lacombe K;Lanoix JP;Makinson A;Martin-Blondel G;Bouadma L;Botelho-Nevers E;Gagneux-Brunon A;Epaulard O;Piroth L;Wallet F;Richard JC;Reuter J;Staub T;Lina B;Noret M;Andrejak C;Lê MP;Peytavin G;Hites M;Costagliola D;Yazdanpanah Y;Burdet C;Mentré F;DisCoVeRy study group
我们评估了洛匹那韦/利托那韦、洛匹那韦/利托那韦-干扰素 (IFN)-β-1a、羟氯喹或瑞德西韦与标准护理（对照）相比，对需要氧气和/或通气支持的 2019 冠状病毒病 (COVID-19) 住院患者的临床、病毒学和安全性结果。我们进行了一项 III 期多中心、开放标签、随机 1:1:1:1:1、适应性、对照试验 (DisCoVeRy)，这是 Solidarity 试验的附加项目 (NCT04315948、EudraCT2020-000936-23)。主要结果是第 15 天时的临床状态，采用 WHO 七点顺序量表进行测量。次要结果包括呼吸道标本中严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的定量以及药代动力学和安全性分析。我们报告了含洛匹那韦/利托那韦组和羟氯喹组的结果，这两个组的试验已提前停止。意向治疗人群包括 583 名参与者——洛匹那韦/利托那韦 (n = 145)、洛匹那韦/利托那韦-IFN-β-1a (n = 145)、羟氯喹 (n = 145)、对照组 (n = 148)——其中 418 名 (71.7%) 为男性，中位年龄为 63 岁 (IQR) 54-71），以及 211 人（36.2%）患有严重疾病。研究治疗第 15 天的临床状态未得到改善：洛匹那韦/利托那韦与对照相比，调整后比值比 (aOR) 0.83，（95% 置信区间 (CI) 0.55–1.26，p = 0.39），洛匹那韦/利托那韦–IFN–β-1a 与对照相比，aOR 0.69（95%CI 0.45–1.04，p 0.08），羟氯喹与对照相比，aOR 0.93（95%CI 0.62-1.41，p 0.75）。未观察到研究性治疗对 SARS-CoV-2 清除有显着影响。洛匹那韦和利托那韦的血浆谷浓度高于预期，而羟氯喹的血浆谷浓度则符合给药方案的预期。分配到含洛匹那韦/利托那韦组的参与者中，严重不良事件的发生率明显更高。在因 COVID-19 住院的成人中，洛匹那韦/利托那韦、洛匹那韦/利托那韦-IFN-β-1a 和羟氯喹既没有改善第 15 天的临床状态，也没有改善呼吸道标本中的 SARS-CoV-2 清除率。
We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir–interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. The intention-to-treat population included 583 participants—lopinavir/ritonavir (n = 145), lopinavir/ritonavir–IFN–β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)—among whom 418 (71.7%) were male, the median age was 63 years (IQR 54–71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55–1.26, p 0.39), lopinavir/ritonavir–IFN–β-1a versus control, aOR 0.69 (95%CI 0.45–1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62–1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir–IFN–β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.
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影响因子：
1.8
作者：
Jung, Byung Hwa;Rezk, Naser L.;Kashuba, Angela D. M.
通讯作者：
Kashuba, Angela D. M.
使用LC-ESI-MS/MS同时定量小鼠血液和组织中其代谢产物的定量：药代动力学研究的应用。
DOI：
10.1016/j.jchromb.2017.11.026
发表时间：
2018-01-01
期刊：
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
影响因子：
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作者：
Chhonker YS;Sleightholm RL;Li J;Oupický D;Murry DJ
通讯作者：
Murry DJ
影响因子：
2.9
作者：
Ofotokun I;Lennox JL;Eaton ME;Ritchie JC;Easley KA;Masalovich SE;Long MC;Acosta EP
通讯作者：
Acosta EP
影响因子：
7.6
作者：
Sallard, Erwan;Lescure, Francois-Xavier;Peiffer-Smadja, Nathan
通讯作者：
Peiffer-Smadja, Nathan
影响因子：
158.5
作者：
Cavalcanti, A. B.;Zampieri, F. G.;Berwanger, O.
通讯作者：
Berwanger, O.