Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxia: an international, randomized, blinded trial

AbstractIMPORTANCEDexamethasone 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.OBJECTIVETo assess the effects of dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxia.DESIGN, SETTING, PARTICIPANTSWe 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.INTERVENTIONSPatients were randomized 1:1 to masked intravenous dexamethasone 12 mg or dexamethasone 6 mg daily for up to 10 days.MAIN OUTCOME MEASURESThe 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).RESULTSAfter 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 RELEVANCEAmong 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 REGISTRATIONClinicalTrials.gov (NCT04509973) and Clinical Trial Registry India (2020/10/028731).</jats:sec

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.

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. Trial Registration ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731

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 (vol 326, pg 1807, 2021)

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 (vol 326, pg 1807, 2021

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 (vol 326, pg 1807, 2021)

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 (vol 326, pg 1807, 2021