TY - JOUR

T1 - 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 The COVID STEROID 2 Randomized Trial

AU - Munch, Marie W.

AU - Myatra, Sheila N.

AU - Vijayaraghavan, Bharath Kumar Tirupakuzhi

AU - Saseedharan, Sanjith

AU - Benfield, Thomas

AU - Wahlin, Rebecka R.

AU - Rasmussen, Bodil S.

AU - Andreasen, Anne Sofie

AU - Poulsen, Lone M.

AU - Cioccari, Luca

AU - Khan, Mohd S.

AU - Kapadia, Farhad

AU - Divatia, Jigeeshu V.

AU - Brochner, Anne C.

AU - Bestle, Morten H.

AU - Helleberg, Marie

AU - Michelsen, Jens

AU - Padmanaban, Ajay

AU - Bose, Neeta

AU - Møller, Anders

AU - Borawake, Kapil

AU - Kristiansen, Klaus T.

AU - Shukla, Urvi

AU - Chew, Michelle S.

AU - Dixit, Subhal

AU - Ulrik, Charlotte S.

AU - Amin, Pravin R.

AU - Chawla, Rajesh

AU - Wamberg, Christian A.

AU - Shah, Mehul S.

AU - Darfelt, Iben S.

AU - Jorgensen, Vibeke L.

AU - Smitt, Margit

AU - Granholm, Anders

AU - Kjær, Maj-Brit N.

AU - Møller, Morten H.

AU - Meyhoff, Tine S.

AU - Vesterlund, Gitte K.

AU - Hammond, Naomi E.

AU - Micallef, Sharon

AU - Bassi, Abhinav

AU - John, Oommen

AU - Jha, Anubhuti

AU - Cronhjort, Maria

AU - Jakob, Stephan M.

AU - Gluud, Christian

AU - Lange, Theis

AU - Kadam, Vaijayanti

AU - Marcussen, Klaus V.

AU - Hollenberg, Jacob

AU - Hedman, Anders

AU - Nielsen, Henrik

AU - Schjorring, Olav L.

AU - Jensen, Marie Q.

AU - Leistner, Jens W.

AU - Jonassen, Trine B.

AU - Kristensen, Camilla M.

AU - Clapp, Esben C.

AU - Hjortso, Carl J. S.

AU - Jensen, Thomas S.

AU - Halstad, Liv S.

AU - Bak, Emilie R. B.

AU - Zaabalawi, Reem

AU - Metcalf-Clausen, Matias

AU - Abdi, Suhayb

AU - Hatley, Emma V.

AU - Aksnes, Tobias S.

AU - Gleipner-Andersen, Emil

AU - Alarcon, Arif F.

AU - Yamin, Gabriel

AU - Heymowski, Adam

AU - Berggren, Anton

AU - La Cour, Kirstine

AU - Weihe, Sarah

AU - Pind, Alison H.

AU - Engstrom, Janus

AU - Jha, Vivekanand

AU - Venkatesh, Balasubramanian

AU - Perner, Anders

PY - 2021

Y1 - 2021

N2 - Importance 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.Objective To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia.Design, Setting, and Participants 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.Interventions 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.Main Outcomes and Measures 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).Results 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]).Conclusions and Relevance 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.

AB - Importance 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.Objective To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia.Design, Setting, and Participants 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.Interventions 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.Main Outcomes and Measures 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).Results 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]).Conclusions and Relevance 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.

U2 - 10.1001/jama.2021.18295

DO - 10.1001/jama.2021.18295

M3 - Journal article

C2 - 34673895

VL - 326

SP - 1807

EP - 1817

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0098-7484

IS - 18

ER -