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Higher vs lower doses of dexamethasone in patients with COVID‐19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan
Author(s) -
Munch MW,
Granholm Anders,
Myatra SN,
Vijayaraghavan BKT,
Cronhjort Maria,
Wahlin RR,
Jakob Stephan M.,
Cioccari Luca,
Kjær MN,
Vesterlund GK,
Meyhoff TS,
Helleberg Marie,
Møller MH,
Benfield Thomas,
Venkatesh Balasubramanian,
Hammond Naomi,
Micallef Sharon,
Bassi Abhinav,
John Oommen,
Jha Vivekanand,
Kristiansen KT,
Ulrik CS,
Jørgensen VL,
Smitt Margit,
Bestle Morten H.,
Andreasen AS,
Poulsen LM,
Rasmussen BS,
Brøchner AC,
Strøm Thomas,
Møller Anders,
Khan MS,
Padmanaban Ajay,
Divatia JV,
Saseedharan Sanjith,
Borawake Kapil,
Kapadia Farhad,
Dixit Subhal,
Chawla Rajesh,
Shukla Urvi,
Amin Pravin,
Chew Michelle S.,
Gluud Christian,
Lange Theis,
Perner Anders
Publication year - 2021
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.13795
Subject(s) - medicine , dexamethasone , dosing , clinical trial , covid-19 , randomized controlled trial , hypoxia (environmental) , adverse effect , corticosteroid , pediatrics , disease , infectious disease (medical specialty) , organic chemistry , chemistry , oxygen
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.