Dataset Information

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

ABSTRACT:

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.

SUBMITTER: Munch MW

PROVIDER: S-EPMC8014264 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

Munch M W MW Granholm Anders A Myatra S N SN Vijayaraghavan Bkt B Cronhjort Maria M Wahlin R R RR Jakob Stephan M SM Cioccari Luca L Kjaer M N MN Vesterlund G K GK Meyhoff T S TS Helleberg Marie M Møller M H MH Benfield Thomas T Venkatesh Balasubramanian B Hammond Naomi N Micallef Sharon S Bassi Abhinav A John Oommen O Jha Vivekanand V Kristiansen K T KT Ulrik C S CS Jørgensen V L VL Smitt Margit M Bestle Morten H MH Andreasen A S AS Poulsen L M LM Rasmussen B S BS Brøchner A C AC Strøm Thomas T Møller Anders A Khan M S MS Padmanaban Ajay A Divatia J V JV Saseedharan Sanjith S Borawake Kapil K Kapadia Farhad F Dixit Subhal S Chawla Rajesh R Shukla Urvi U Amin Pravin P Chew Michelle S MS Gluud Christian C Lange Theis T Perner Anders A

Acta anaesthesiologica Scandinavica 20210309 6

<h4>Background</h4>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- ...[more]

PMID: 33583034

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Project description:ImportanceSupplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial.ObjectiveTo assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU).Design, setting, and participantsMulticenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023.InterventionsPatients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU.Main outcomes and measuresThe primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days.ResultsOf 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital.Conclusion and relevanceIn adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg.Trial registrationClinicalTrials.gov Identifier: NCT04425031.

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Project description:ImportanceProstate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility.ObjectiveTo explore differences in risk of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts.Design, setting, and participantsThis cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in 2 prospective cohort studies in Sweden and the US, the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS), followed up from 1991 to 2019. Data were analyzed between April 2023 and April 2024.ExposuresMen were categorized according to modifiable lifestyle behaviors and genetic risk. A polygenic risk score above the median or a family history of cancer defined men at higher genetic risk (67% of the study population); the remaining men were categorized as being at lower genetic risk.Main outcomes and measuresProstate cancer death analyzed using time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age.ResultsAmong the 19 607 men included for analysis, the median (IQR) age at inclusion was 59.0 (53.0-64.7) years (MDCS) and 65.1 (58.0-71.8) years (HPFS). During follow-up, 107 early (by age 75 years) and 337 late (after age 75 years) prostate cancer deaths were observed. Compared with men at lower genetic risk, men at higher genetic risk had increased rates of both early (HR, 3.26; 95% CI, 1.82-5.84) and late (HR, 2.26; 95% CI, 1.70-3.01) prostate cancer death, and higher lifetime risks of prostate cancer death (3.1% vs 1.3% [MDCS] and 2.3% vs 0.6% [HPFS]). Men at higher genetic risk accounted for 94 of 107 early prostate cancer deaths (88%), of which 36% (95% CI, 12%-60%) were estimated to be preventable through adherence to behaviors associated with a healthy lifestyle (not smoking, healthy weight, high physical activity, and a healthy diet).Conclusions and relevanceIn this 20-year follow-up study, men with a genetic predisposition accounted for the vast majority of early prostate cancer deaths, of which one-third were estimated to be preventable. This suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.

Dataset Information

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

Background

Methods

Discussion

Publications

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

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