Namilumab or infliximab compared to standard of care in hospitalised patients with COVID-19 (CATALYST): a phase 2 randomised adaptive trial
Namilumab or infliximab compared to standard of care in hospitalised patients with COVID-19 (CATALYST): a phase 2 randomised adaptive trial
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纳米鲁单抗或英夫利昔单抗与 COVID-19 住院患者护理标准的比较 (CATALYST)：一项 2 期随机适应性试验
DOI：
10.1101/2021.06.02.21258204
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Fisher B
中科院分区：
文献类型：
--
作者：
Fisher B
背景炎症调节失调与2019年冠状病毒病（COVID-19）的不良结局有关。我们评估了纳米单抗（一种粒细胞-巨噬细胞集落刺激因子抑制剂）和英夫利昔单抗（一种肿瘤坏死因子抑制剂）在住院的COVID-19患者中的疗效，以优先考虑3期试验的药物。适应性2期概念验证试验（CATALYST），我们在9家英国医院招募了年龄≥ 16岁的COVID-19肺炎和C反应蛋白（CRP）≥ 40 mg/L的住院患者。参与者被随机分配到常规护理，或常规护理加单次150 mg静脉注射剂量的那木单抗（150 mg）或英夫利西单抗（5 mg/kg）。按病房与ICU对随机化进行分层。主要终点是使用贝叶斯多水平模型分析，通过CRP随时间测量，与对照组相比，干预组的炎症改善。ISRCTN登记号40580903。结果在2020年6月15日至2021年2月18日期间，我们随机分配了146名参与者：54名接受常规治疗，57名接受那美鲁单抗，35名接受英夫利昔单抗。随着时间的推移，那米诺单抗和英夫利西单抗在降低CRP方面上级常规治疗的概率分别为97%和15%。在病房和ICU患者中观察到一致的效果，并与临床结局一致，因此，ICU和病房患者在第28天出院的概率（WHO 1-3级）分别为47%和64%，而接受那木单抗治疗的患者分别为66%和77%。在30/55例（54.5%）Nam患者中发生了134起不良事件，而在29/54例（53.7%）常规治疗患者中发生了145起不良事件。20/29例（69.0%）英夫利西单抗患者发生102起事件，而17/34例（50.0%）常规治疗患者发生112起事件。解释纳米单抗而非英夫利西单抗证明了概念验证证据，可减轻COVID-19肺炎住院患者的炎症，这与次要临床结局一致。纳米尤单抗应被COVID-19基金医学研究理事会优先用于进一步调查。
BackgroundDysregulated inflammation is associated with poor outcomes in Coronavirus disease 2019 (COVID-19). We assessed the efficacy of namilumab, a granulocyte-macrophage colony-stimulating factor inhibitor and infliximab, a tumour necrosis factor inhibitor in hospitalised patients with COVID-19 in order to prioritise agents for phase 3 trials.MethodsIn this randomised, multi-arm, parallel group, open label, adaptive phase 2 proof-of-concept trial (CATALYST) we recruited hospitalised patients ≥ 16 years with COVID-19 pneumonia and C-reactive protein (CRP) ≥ 40mg/L in nine UK hospitals. Participants were randomly allocated with equal probability to usual care, or usual care plus a single 150mg intravenous dose of namilumab (150mg) or infliximab (5mg/kg). Randomisation was stratified for ward versus ICU. The primary endpoint was improvement in inflammation in intervention arms compared to control as measured by CRP over time, analysed using Bayesian multi-level models. ISRCTN registry number 40580903.FindingsBetween 15thJune 2020 and 18thFebruary 2021 we randomised 146 participants: 54 to usual care, 57 to namilumab and 35 to infliximab. The probabilities that namilumab and infliximab were superior to usual care in reducing CRP over time were 97% and 15% respectively. Consistent effects were seen in ward and ICU patients and aligned with clinical outcomes, such that the probability of discharge (WHO levels 1-3) at day 28 was 47% and 64% for ICU and ward patients on usual care, versus 66% and 77% for patients treated with namilumab. 134 adverse events occurred in 30/55 (54.5%) namilumab patients compared to 145 in 29/54 (53.7%) usual care patients. 102 events occurred in 20/29 (69.0%) infliximab patients versus 112 events in 17/34 (50.0%) usual care patients.InterpretationNamilumab, but not infliximab, demonstrated proof-of-concept evidence for reduction in inflammation in hospitalised patients with COVID-19 pneumonia which was consistent with secondary clinical outcomes. Namilumab should be prioritised for further investigation in COVID-19.FundingMedical Research Council.
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影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
效果：初步报告
DOI：
--
发表时间：
2012
期刊：
影响因子：
--
作者：
Yayota;M.;Kato;A.;Ohtani;S.
通讯作者：
S.
粒细胞巨噬细胞集落刺激因子诱导脓毒症患者单核细胞活化并恢复呼吸爆发活性。
DOI：
10.1086/513802
发表时间：
1998
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Marc A. Williams;S. White;Jessica J. Miller;Christopher C. Toner;S. Withington;Adrian C. Newland;Stephen M. Kelsey
通讯作者：
Stephen M. Kelsey
影响因子：
4.6
作者：
Daamen AR;Bachali P;Owen KA;Kingsmore KM;Hubbard EL;Labonte AC;Robl R;Shrotri S;Grammer AC;Lipsky PE
通讯作者：
Lipsky PE
影响因子：
25.4
作者：
De Luca, Giacomo;Cavalli, Giulio;Dagna, Lorenzo
通讯作者：
Dagna, Lorenzo