Heterogeneous treatment effects of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia—Post hoc exploratory analyses of the COVID STEROID 2 trial
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Background: Corticosteroids improve outcomes in patients with severe COVID-19. In the COVID STEROID 2 randomised clinical trial, we found high probabilities of benefit with dexamethasone 12 versus 6 mg daily. While no statistically significant heterogeneity in treatment effects (HTE) was found in the conventional, dichotomous subgroup analyses, these analyses have limitations, and HTE could still exist. Methods: We assessed whether HTE was present for days alive without life support and mortality at Day 90 in the trial according to baseline age, weight, number of comorbidities, category of respiratory failure (type of respiratory support system and oxygen requirements) and predicted risk of mortality using an internal prediction model. We used flexible models for continuous variables and logistic regressions for categorical variables without dichotomisation of the baseline variables of interest. HTE was assessed both visually and with p and S values from likelihood ratio tests. Results: There was no strong evidence for substantial HTE on either outcome according to any of the baseline variables assessed with all p values >.37 (and all S values <1.43) in the planned analyses and no convincingly strong visual indications of HTE. Conclusions: We found no strong evidence for HTE with 12 versus 6 mg dexamethasone daily on days alive without life support or mortality at Day 90 in patients with COVID-19 and severe hypoxaemia, although these results cannot rule out HTE either.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Acta Anaesthesiologica Scandinavica |
| Vol/bind | 67 |
| Udgave nummer | 2 |
| Sider (fra-til) | 195-205 |
| Antal sider | 11 |
| ISSN | 0001-5172 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The COVID STEROID 2 trial was funded by Novo Nordisk Foundation and the Research Council of Rigshospitalet. The funders had no role in the design, conduct, analyses or reporting of the trial or this secondary study.
Funding Information:
Anders Granholm, Marie Warrer Munch, Morten Hylander Møller and Anders Perner are affiliated with the Department of Intensive Care at Rigshospitalet—Copenhagen University Hospital, which has received funding for other projects from the Novo Nordisk Foundation, Sygeforsikringen ‘danmark’, Pfizer and Fresenius Kabi, and conducts contract research for AM‐Pharma. Vivekanand Jha has received grant funding from GSK, Baxter Healthcare and Biocon and has received honoraria from Bayer, AstraZeneca, Boeringer Ingelheim, NephroPlus and Zydus Cadilla, under the policy of all honoraria being paid to the organisation. Stephan M. Jakob reports that the Department of Intensive Care Medicine, University Hospital Bern, has or has had in the past, research and development/consulting contracts with Edwards Lifesciences Services GmbH, Phagenesis Limited, Nestlé and Cytel Inc. The money was paid into a departmental fund, Dr Jakob did not receive any financial gain. The Department of Intensive Care Medicine, University Hospital Bern has received in the past unrestricted educational grants from the following organisations for organising bi‐annual postgraduate courses in the fields of critical care ultrasound, management of ECMO and mechanical ventilation: Pierre Fabre Pharma AG (formerly known as RobaPharm), Pfizer AG, Bard Medica S.A., Abbott AG, Anandic Medical Systems, PanGas AG Healthcare, Orion Pharma, Bracco, Edwards Lifesciences AG, Hamilton Medical AG, Fresenius Kabi (Schweiz) AG, Getinge Group Maquet AG, Dräger Schweiz AG and Teleflex Medical GmbH.
Publisher Copyright:
© 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.
ID: 338308809