在 COVID-19 肺炎中延长高剂量甲泼尼龙与常规地塞米松：一项随机对照试验 (MEDEAS),European Respiratory Journal

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在 COVID-19 肺炎中延长高剂量甲泼尼龙与常规地塞米松：一项随机对照试验 (MEDEAS)
European Respiratory Journal ( IF 16.6 ) Pub Date : 2023-04-20 , DOI: 10.1183/13993003.01514-2022
Francesco Salton _{1,

2} , Paola Confalonieri _{2,

3} , Stefano Centanni ₄ , Michele Mondoni ₄ , Nicola Petrosillo ₅ , Paolo Bonfanti _{6,

7} , Giuseppe Lapadula _{6,

7} , Donato Lacedonia ₈ , Antonio Voza ₉ , Nicoletta Carpenè ₁₀ , Marcella Montico ₃ , Nicolò Reccardini _{2,

3} , Gianfranco Umberto Meduri ₁₁ , Barbara Ruaro _{2,

3} , , Marco Confalonieri _{2,

3} , , Gloria Maria Citton , Giulia Lapadula , Chiara Bozzi , Stefano Tavano , Riccardo Pozzan , Alessia Giovanna Andrisano , Mohamad Jaber , Marco Mari , Liliana Trotta , Lucrezia Mondini , Mariangela Barbieri , Luca Ruggero , Caterina Antonaglia , Sara Soave , Chiara Torregiani , Tjaša Bogatec , Andrea Baccelli , Giulia Nalesso , Beatrice Re , Stefano Pavesi , Maria Pia Foschino Barbaro , Antonella Giuliani , Claudia Ravaglia , Venerino Poletti , Raffaele Scala , Luca Guidelli , Nicoletta Golfi , Andrea Vianello , Alessia Achille , Paolo Lucernoni , Anna Talia Gaccione , Micaela Romagnoli , Alessia Fraccaro , Nicola Malacchini , Mario Malerba , Beatrice Ragnoli , Alessandro Sanduzzi Zamparelli , Marialuisa Bocchino , Francesco Blasi , Maura Spotti , Carmen Miele , Federica Piedepalumbo , Ivan Barone , Stefano Baglioni , Meridiana Dodaj , Cosimo Franco , Francesco Andrani , Angelo Mangia , Annalisa Mancini , Laura Carrozzi , Annalisa Rafanelli , Elisabetta Casto , Paola Rogliani , Josuel Ora , Giovanna Elisiana Carpagnano , Valentina Di Lecce , Mario Tamburrini , Alberto Papi , Marco Contoli , Roberto Luzzati , Marta Zatta , Stefano Di Bella , Emanuela Caraffa , Daniela Francisci , Andrea Tosti , Carlo Pallotto , Francesco Giuseppe De Rosa , Alessio Pecori , Marta Franceschini , Massimiliano Carlin , Valentina Orsini , Anna Spolti , Marta Inannace , Teresa Santantonio , Rossella Meli , Sara Sauro , Carlo Fedeli , Elisabetta Mangini , Gianni Biolo , Alessio Nunnari , Antonello Pietrangelo , Elena Corradini , Davide Bocchi , Chiara Boarini , Antonella Zucchetto , Simone Lanini

Affiliation

Department of Pulmonology, University Hospital of Cattinara, Trieste, Italy
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
Department of Pulmonology, University Hospital of Cattinara, Trieste, Italy.
Department of Health Sciences - Università degli Studi di Milano, Respiratory Unit ASST Santi Paolo e Carlo, Milan, Italy.
Infection Prevention and Control - Infectious Disease Service, Foundation University Hospital Campus Bio-Medico, Rome, Italy.
Infectious Diseases Unit, ASST Monza, San Gerardo Hospital, Monza, Italy.
School of Medicine, University of Milan-Bicocca, Milan, Italy.
Department of Medical and Surgical Sciences - University of Foggia, Policlinico Riuniti, Foggia, Italy.
Emergency Medicine Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
Pulmonary Unit, Cardio-Thoracic and Vascular Department, University Hospital of Pisa, Pisa, Italy.
Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.

背景

全身性炎症失调是导致 2019 年严重冠状病毒病 (COVID-19) 肺炎死亡的主要原因。目前的指南支持 7-10 天疗程的任何糖皮质激素，相当于每天 6 毫克地塞米松。缺乏具有更高剂量和更长干预持续时间的比较随机对照试验 (RCT)。

方法

我们进行了一项多中心、开放标签的随机对照试验，以研究甲基泼尼松龙 80 毫克每天连续输注 8 天，然后缓慢减量与地塞米松 6 毫克，每天一次，最多 10 天在需要氧气或无创呼吸的成年 COVID-19 肺炎患者中的疗效支持。主要结果是降低 28 天死亡率。次要结果是第 28 天无机械通气天数、转诊重症监护病房 (ICU) 的需要、住院时间、气管切开术的需要以及 C 反应蛋白 (CRP) 水平的变化、动脉氧分压/吸入氧分率 ( P _{aO ₂} / F _{IO ₂} ) 比值和第 3、7 和 14 天的世界卫生组织临床进展量表。

结果

包括 677 名随机患者。结果报告为甲泼尼龙 (n=337)与地塞米松 (n=340)。到第 28 天，死亡率（35 (10.4%)对41 (12.1%)；p=0.49）和无机械通气天数中位数（中位数（四分位数间距 (IQR)）23 (14)对24 (16) 天；p=0.49)。41 例 (12.2%)与45 例 (13.2%) (p=0.68)需要 ICU 转诊，8 例 (2.4%)与9 例 (2.6%) 需要气管切开术 (p=0.82)。甲基强的松龙组的幸存者需要更长的中位 (IQR) 住院时间（15 (11)与14 (11) 天；p=0.005）并且 CRP 水平有所改善，但P _{aO没有改善₂} / F _{IO ₂}比率，第 7 天和第 14 天。在预先指定的时间点，疾病进展没有差异。

结论

与 COVID-19 肺炎中的常规地塞米松相比，延长、更高剂量的甲泼尼龙并没有降低 28 天时的死亡率。

"点击查看英文标题和摘要"

Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Background

Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7–10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking.

Methods

We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P_aO₂/F_IO₂) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14.

Results

677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P_aO₂/F_IO₂ ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points.