Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia
Authors: Lene Russell, Kis Rønn Uhre, Ann Louise Syraach Lindgaard, Jette Fredlund Degn, Mik Wetterslev, Praleene Sivapalan, Carl Thomas Anthon, Vibe Sommer Mikkelsen, Louise Colette la Porta, Thomas Steen Jensen, Charlotte Kastberg Levin, Gitte Kronborg, Rikke Krogh-Madsen, Ronni Thermann Reitz Plovsing, Helene Brix, Martin Schønemann-Lund, Lone Valbjørn, Sanne Lauritzen, Ellen Bjerre Koch, Valdemar Oskar Ingemann Sørensen, Hans Eric Sebastian Seitz-Rasmussen, Frederik Heiberg Bestle, Nina Christine Andersen-Ranberg, Camilla Bekker Mortensen, Cecilie Bauer Derby, Emma Ritsmer Stormholt, Yifei Cao, Thomas Steen Strøm, Eva Lærkner, Christine Gilberg, Michella Poulsen, Hanne Tanghus Olsen, Charlotte Rosenkilde, Trine Haberlandt, Lars Peter Kloster Andersen, Diana Bertelsen Jensen, Mia Charlotte Krogh Hansen, Søren Rosborg Aagaard, Stine Rom Vestergaard, Anne-Marie Gellert Bunzel, Rine Moulvad Siegumfeldt, Thomas Lass Klitgaard, Kirsten Uldal Krejberg, Henrik Nielsen, Evangeline Elvira, Hilda Nirmala Kumari, Jayanthi Swaminathan, K Arun Chander, N Ganesh Rajan, Sona Thomas, Ann Thomas, Vishnu Odankadummai, Anu M Antony, Atul P Kulkarni, Nishanth Baliga, Nirmalyo Lodh, Swapna C Vijayakumaran, Kushal Kalvit, Tarun Sahu, Vijaya P Patil, Amol T Kothekar, Shilpushp J Bhosale, Manoj Gorade, Anjana M Shrivastava, Jare Jagannath Uddhavrao, Ritika Sharma, Jyotsna Mali, H R Niranjan, Celine Lobo, Vaishali Neve, Deepika Maurya, Mahesh Salunke, Santiswaroop Pattanaik, Akhliesh Agrawal, Ashit Hegde, Rishi Kumar Badgurjar, Binit N Jhaveri, Digamber B Sarje, H.J Ananda, Bitan Sen, C.M Ambily, Emilin P Jose, Vaijayanti Kadam, Annapurna Chiluka, Rohit Kuril, Elizabeth Mathew, Survana Shirsekar, Sudha Kansal, Rinku Dahiya, Vijaya Kumar Thakur, Rajni Tewatia, Savita Rawat, Harsh Tyagi, Meenakshi Bhakare, Chinmayee Bhise, Amit Girme, Lini T Kunjumon, Merlin Jose, Nikunj Sharma, Amol Bali, Mayr Patel, Nirankar Bhutaka, Edwin Pathrose, Gopal Goyal, Riya Baby, Roshini Fernandez, Pradip K Bhattacharya, Srishti Kindo, A. Aaditya, Kritiaka Raj, Aastha Poddar, Aftab Ansari, Mustaque Alam, Vijay Khandagale, Satish Sarode, Sanesh Garde, Sushant Shinde, Narndev Jagtap, Chagan Khartode, Amit Palange, Aishwarya Pawar, Mayuri Mulay, Simrah Pirzade, Mohini Jagtap, Balbhim Rathod, Dhara Tanna, Kinjal Chaudhary, Shubhangi Deshpande, Rikin Raj, Sourab Ambapkar, Shobhana Ambapkar, Mukund Penurkar, Amit Sambare, Ravindra Joshi, Bhushan Kinolkar, Tarannum Aslam Shaikh, Helen Didriksson, Carina Jönsson, Gunilla Gagnö, David Zacharias, Margaret Lynn Jong, Marianne Roth, Rachelle Mader, Laureta Fazlija, Manuela Akaltan, Anjana Eichenberger, Gion Rüegg, Tatjana Dill, Bruno Schoenmaekers, Ashwani Kumar, Dorrilyn Rajbhandari, Sumaiya Arfin, Nikita Bathla, Rajesh Joshi, Mallikarjuna Kunigari, Marie W. Munch, Sheila N. Myatra, Bharath Kumar Tirupakuzhi Vijayaraghavan, 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, Anders Perner
Journal: JAMA (2021)

A 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.To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia.A 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.Patients 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.The 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).Of 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]).Among 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.ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.