TY - JOUR

T1 - Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial

T2 - Protocol and statistical analysis plan

AU - Warrer Munch, Marie

AU - Granholm, Anders

AU - Nainan Myatra, Sheila

AU - Kumar Tirupakuzhi Vijayaraghavan, Bharath

AU - Cronhjort, Maria

AU - Rubenson Wahlin, Rebecka

AU - Jakob, Stephan M.

AU - Cioccari, Luca

AU - Nørregaard Kjær, Maj Brit

AU - Kingo Vesterlund, Gitte

AU - Sylvest Meyhoff, Tine

AU - Helleberg, Marie

AU - Hylander Møller, Morten

AU - Benfield, Thomas

AU - Venkatesh, Balasubramanian

AU - Hammond, Naomi

AU - Micallef, Sharon

AU - Bassi, Abhinav

AU - John, Oommen

AU - Jha, Vivekanand

AU - Tjelle Kristiansen, Klaus

AU - Suppli Ulrik, Charlotte

AU - Lind Jørgensen, Vibeke

AU - Smitt, Margit

AU - Bestle, Morten H.

AU - Sofie Andreasen, Anne

AU - Musaeus Poulsen, Lone

AU - Steen Rasmussen, Bodil

AU - Craveiro Brøchner, Anne

AU - Strøm, Thomas

AU - Møller, Anders

AU - Saif Khan, Mohd

AU - Padmanaban, Ajay

AU - Vasishtha Divatia, Jigeeshu

AU - Saseedharan, Sanjith

AU - Borawake, Kapil

AU - Kapadia, Farhad

AU - Dixit, Subhal

AU - Chawla, Rajesh

AU - Shukla, Urvi

AU - Amin, Pravin

AU - Chew, Michelle S.

AU - Gluud, Christian

AU - Lange, Theis

AU - Perner, Anders

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1111/aas.13795

DO - 10.1111/aas.13795

M3 - Journal article

C2 - 33583034

AN - SCOPUS:85102303150

VL - 65

SP - 834

EP - 845

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 6

ER -