Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.
Anti-Inflammatory Agents
/ administration & dosage
COVID-19
/ complications
Denmark
Dexamethasone
/ administration & dosage
Dose-Response Relationship, Drug
Double-Blind Method
Hospital Mortality
Humans
Hydrocortisone
/ therapeutic use
Hypoxia
/ drug therapy
India
Life Support Care
/ statistics & numerical data
Pandemics
Practice Patterns, Physicians'
/ statistics & numerical data
Quality of Life
Randomized Controlled Trials as Topic
/ methods
SARS-CoV-2
Survival Analysis
Sweden
Switzerland
COVID-19 Drug Treatment
Journal
Acta anaesthesiologica Scandinavica
ISSN: 1399-6576
Titre abrégé: Acta Anaesthesiol Scand
Pays: England
ID NLM: 0370270
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
28
01
2021
accepted:
31
01
2021
pubmed:
15
2
2021
medline:
12
6
2021
entrez:
14
2
2021
Statut:
ppublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 33583034
doi: 10.1111/aas.13795
pmc: PMC8014264
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Dexamethasone
7S5I7G3JQL
Hydrocortisone
WI4X0X7BPJ
Types de publication
Clinical Trial Protocol
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
834-845Subventions
Organisme : Rigshospitalet
ID : E-22703-06
Organisme : Novo Nordisk Fonden
ID : 0062998
Informations de copyright
© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Références
JAMA. 2020 Mar 17;323(11):1061-1069
pubmed: 32031570
JAMA. 2020 Oct 6;324(13):1330-1341
pubmed: 32876694
Qual Life Res. 2011 Dec;20(10):1727-36
pubmed: 21479777
BMC Musculoskelet Disord. 2016 Jul 16;17:293
pubmed: 27424036
Lancet Respir Med. 2020 Mar;8(3):267-276
pubmed: 32043986
Acta Anaesthesiol Scand. 2017 Aug;61(7):859-868
pubmed: 28608496
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Ann Intern Med. 2013 Feb 5;158(3):200-7
pubmed: 23295957
J Pharmacol Pharmacother. 2010 Jul;1(2):100-7
pubmed: 21350618
Acta Anaesthesiol Scand. 2021 Jul;65(6):834-845
pubmed: 33583034
BMJ. 2020 May 29;369:m1996
pubmed: 32471884
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
N Engl J Med. 2020 May 7;382(19):1787-1799
pubmed: 32187464
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Clin Infect Dis. 2020 Apr 27;:
pubmed: 32338708
Stat Med. 2012 Feb 20;31(4):328-40
pubmed: 22139891
BMC Med Res Methodol. 2017 Dec 6;17(1):162
pubmed: 29207961
J Antimicrob Chemother. 2001 Jun;47(6):841-53
pubmed: 11389117
Nat Rev Immunol. 2020 Jun;20(6):355-362
pubmed: 32376901
JAMA Intern Med. 2020 Jul 1;180(7):934-943
pubmed: 32167524
Biometrics. 1979 Sep;35(3):549-56
pubmed: 497341