• COVID STEROID 2 Trial Group, Marie W Munch, Sheila N Myatra, VijayaraghavanBharath Kumar TirupakuzhiBKTApollo Hospitals, Chennai, India., Sanjith Saseedharan, Thomas Benfield, Rebecka R Wahlin, Bodil S Rasmussen, Anne Sofie Andreasen, Lone M Poulsen, Luca Cioccari, Mohd S Khan, Farhad Kapadia, Jigeeshu V Divatia, Anne C Brøchner, Morten H Bestle, Marie Helleberg, Jens Michelsen, Ajay Padmanaban, Neeta Bose, Anders Møller, Kapil Borawake, Klaus T Kristiansen, Urvi Shukla, Michelle S Chew, Subhal Dixit, Charlotte S Ulrik, Pravin R Amin, Rajesh Chawla, Christian A Wamberg, Mehul S Shah, Iben S Darfelt, Vibeke L Jørgensen, Margit Smitt, Anders Granholm, Maj-Brit N Kjær, Morten H Møller, Tine S Meyhoff, Gitte K Vesterlund, Naomi E Hammond, Sharon Micallef, Abhinav Bassi, Oommen John, Anubhuti Jha, Maria Cronhjort, Stephan M Jakob, Christian Gluud, Theis Lange, Vaijayanti Kadam, Klaus V Marcussen, Jacob Hollenberg, Anders Hedman, Henrik Nielsen, Olav L Schjørring, Marie Q Jensen, Jens W Leistner, Trine B Jonassen, Camilla M Kristensen, Esben C Clapp, Carl J S Hjortsø, Thomas S Jensen, Liv S Halstad, Emilie R B Bak, Reem Zaabalawi, Matias Metcalf-Clausen, Suhayb Abdi, Emma V Hatley, Tobias S Aksnes, Emil Gleipner-Andersen, Arif F Alarcón, Gabriel Yamin, Adam Heymowski, Anton Berggren, Kirstine La Cour, Sarah Weihe, Alison H Pind, Janus Engstrøm, Vivekanand Jha, Balasubramanian Venkatesh, and Anders Perner.
• Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
• JAMA. 2021 Nov 9; 326 (18): 180718171807-1817.

ImportanceA daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease.ObjectiveTo assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia.Design, Setting, And ParticipantsA multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021.InterventionsPatients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days.Main Outcomes And MeasuresThe primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days).ResultsOf the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]).Conclusions And RelevanceAmong patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.Trial RegistrationClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.

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