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Background: The efficacy and safety of awake prone positioning (APP) in hypoxemic patients with coronavirus disease 2019 (COVID-19) is unclear. Aim(s): To evaluate the efficacy and safety of APP in non-intubated adults with COVID-19. Method(s): We performed a pragmatic, international, randomized trial at 21 centers in Canada, Saudi Arabia, Kuwait, and the United States between May 19, 2020, and May 18, 2021. Eligible patients were hospitalized adults with COVID-19 requiring >40% oxygen. Patients were randomized to APP (n=205) or usual care (n=195). The primary outcome was intubation by day 30. Secondary outcomes included mortality at 60 days, ventilation-free days at 30 days, intensive care unit (ICU) and hospital-free days at 60 days, adverse events, and serious adverse events. Result(s): Patients in the APP group proned for a median of 4.8 hours per day (IQR 1.8 to 8.0) in the first 4 days. By day 30, 70/205 patients (34.1%) in the APP group and 79/195 (40.5%) in the control group were intubated (hazard ratio [HR] 0.81;95% confidence interval [CI] 0.59 to 1.12). APP did not reduce mortality at 60 days (HR 0.93;95% CI 0.62 to 1.40) and had no effect on days alive invasively or noninvasively ventilated at 30 days, or days out of ICU or hospital at 60 days. There were no serious adverse events in either group. A prespecified subgroup analysis suggested that APP reduced intubation among patients with SpO2:FiO2 >150 (HR of 0.44, 95% CI 0.23 to 0.87) but not among patients with SpO2:FiO2 <150 (HR 1.02;95% CI 0.70 to 1.48;P-interaction= 0.03). Conclusion(s): APP did not significantly reduce intubation at 30 days or mortality at 60 days overall, but may be effective in patients with SpO2:FiO2 >150.
RESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.