Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxia: an international, randomized, blinded trial
Authors: Munch Marie W. , Myatra Sheila N. , Tirupakuzhi Vijayaraghavan Bharath Kumar , Saseedharan Sanjith , Benfield Thomas , Wahlin Rebecka R. , Rasmussen Bodil S. , Andreasen Anne Sofie , Poulsen Lone M. , Cioccari Luca , Khan Mohd S. , Kapadia Farhad , Divatia Jigeeshu V. , Brøchner Anne C. , Bestle Morten H. , Helleberg Marie , Michelsen Jens , Padmanaban Ajay , Bose Neeta , Møller Anders , Borawake Kapil , Kristiansen Klaus T. , Shukla Urvi , Chew Michelle S. , Dixit Subhal , Ulrik Charlotte S. , Amin Pravin R. , Chawla Rajesh , Wamberg Christian A. , Shah Mehul S. , Darfelt Iben S. , Jørgensen Vibeke L. , Smitt Margit , Granholm Anders , Kjær Maj-Brit N. , Møller Morten H. , Meyhoff Tine S. , Vesterlund Gitte K. , Hammond Naomi E. , Micallef Sharon , Bassi Abhinav , John Oommen , Jha Anubhuti , Cronhjort Maria , Jakob Stephan M. , Gluud Christian , Lange Theis , Kadam Vaijayanti , Marcussen Klaus V. , Hollenberg Jacob , Hedman Anders , Nielsen Henrik , Schjørring Olav L. , Jensen Marie Q. , Leistner Jens W. , Jonassen Trine B. , Kristensen Camilla M. , Clapp Esben C. , Hjortsø Carl J. S. , Jensen Thomas S. , Halstad Liv S. , Bak Emilie R. B. , Zaabalawi Reem , Metcalf-Clausen Matias , Abdi Suhayb , Hatley Emma V. , Aksnes Tobias S. , Gleipner-Andersen Emil , Alarcón Arif F. , Yamin Gabriel , Heymowski Adam , Berggren Anton , Cour Kirstine la , Weihe Sarah , Pind Alison H. , Engstrøm Janus , Jha Vivekanand , Venkatesh Balasubramanian , Perner Anders ,   COVID STEROID 2 trial collaborators
Published: July 2021

IMPORTANCE

Dexamethasone 6 mg daily 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 dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxia.

DESIGN, SETTING, PARTICIPANTS

We conducted a parallel-grouped, stratified, blinded randomized trial including 1000 adults with confirmed COVID-19 receiving at least 10 l/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India from August 2020 to May 2021.

INTERVENTIONS

Patients were randomized 1:1 to masked intravenous dexamethasone 12 mg or dexamethasone 6 mg daily for up to 10 days.

MAIN OUTCOME MEASURES

The primary outcome was the number of days alive without life support (i.e. invasive mechanical ventilation, circulatory support or renal replacement therapy) at 28 days. The primary analysis was adjusted for stratification variables (site, age below 70 years and invasive mechanical ventilation).

RESULTS

After exclusion of 18 patients who withdrew consent, there were 982 patients (613 in Europe, 369 in India) in the intention-to-treat population. We had primary outcome data for 971 patients; 491 assigned to dexamethasone 12 mg and 480 assigned to dexamethasone 6 mg. The median number of days alive without life support was 22.0 days (interquartile range 6.0-28.0) in the 12 mg group and 20.5 days (4.0-28.0) in the 6 mg group (adjusted mean difference 1.3 days, 95% confidence interval (CI), 0.0-2.6; P=0.066). Mortality at 28 days was 27.1% and 32.3% in patients assigned to 12 mg and 6 mg, respectively (adjusted relative risk 0.86, 99% CI, 0.68-1.08). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% versus 13.2% of patients in the 12 mg group and 6 mg group, respectively (adjusted relative risk 0.85, 99% CI, 0.55-1.32).

CONCLUSIONS AND RELEVANCE

Among patients with COVID-19 and severe hypoxia, dexamethasone 12 mg did not result in statistically significantly more days alive without life support at 28 days than dexamethasone 6 mg. However, the confidence interval around the point estimate should be considered when interpreting the results of this trial.

TRIAL REGISTRATION

ClinicalTrials.gov (NCT04509973) and Clinical Trial Registry India (2020/10/028731).