Heterogenous treatment effects of dexamethasone 12 mg vs. 6 mg in patients with COVID-19 and severe hypoxaemia - post hoc exploratory analyses of the COVID STEROID 2 trial.

Granholm, Anders; Munch, Marie Warrer; Andersen-Ranberg, Nina; Myatra, Sheila Nainan; Vijayaraghavan, Bharath Kumar Tirupakuzhi; Venkatesh, Balasubramanian; Jha, Vivekanand; Rubenson, Rebecka Wahlin; Jakob, Stephan M; Cioccari, Luca; Møller, Morten Hylander; Perner, Anders (2023). Heterogenous treatment effects of dexamethasone 12 mg vs. 6 mg in patients with COVID-19 and severe hypoxaemia - post hoc exploratory analyses of the COVID STEROID 2 trial. Acta anaesthesiologica Scandinavica, 67(2), pp. 195-205. Wiley 10.1111/aas.14167

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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 mg vs. 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 were 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 >0.37 (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 vs. 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. This article is protected by copyright. All rights reserved.

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