Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct 4:20:100293.
doi: 10.1016/j.lansea.2023.100293. eCollection 2024 Jan.

Heterogeneity of treatment effect of higher dose dexamethasone by geographic region (Europe vs. India) in patients with COVID-19 and severe hypoxemia - a post hoc evaluation of the COVID STEROID 2 trial

Bharath Kumar Tirupakuzhi Vijayaraghavan  1 , Anders Granholm  2 , Sheila N Myatra  3 , Vivekanand Jha  4   5   6 , Naomi Hammond  7   8 , Sharon Micallef  7 , Marie Warrer Munch  2 , Maj-Brit N Kjær  2 , Morten Hylander Møller  2 , Theis Lange  9 , Anders Perner  2 , Balasubramanian Venkatesh  7 ; COVID-STEROID 2 collaborators
Collaborators, Affiliations

Heterogeneity of treatment effect of higher dose dexamethasone by geographic region (Europe vs. India) in patients with COVID-19 and severe hypoxemia - a post hoc evaluation of the COVID STEROID 2 trial

Bharath Kumar Tirupakuzhi Vijayaraghavan et al. Lancet Reg Health Southeast Asia. .

Abstract

Background: In the COVID-STEROID 2 trial there was suggestion of heterogeneity of treatment effects (HTE) between patients enrolled from Europe vs. India on the primary outcome. Whether there was HTE for the remaining patient-centred outcomes is unclear.

Methods: In this post hoc analysis of the COVID-STEROID 2 trial, which compared 12 mg vs. 6 mg dexamethasone in adults with COVID-19 and severe hypoxemia, we evaluated HTE by geographical region (Europe vs. India) for secondary outcomes with analyses adjusted for stratification variables. Results are presented as risk differences (RDs) or mean differences (MDs) with 99% confidence intervals (CIs) and P-values from interaction tests.

Findings: There were differences in mortality at day 28 (RD for Europe -8.3% (99% CI: -17.7 to 1.0) vs. India 0.1% (99% CI: -10.0 to 10.0)), mortality at day 90 (RD for Europe -7.4% (99% CI: -17.1 to 2.0) vs. India -1.4% (99% CI: -12.8 to 9.8)), mortality at day 180 (RD for Europe -6.7% (99% CI: -16.4 to 2.9) vs. India -1.0% (99% CI: -12.3 to 10.3)), and number of days alive without life support at day 90 (MD for Europe 6.1 days (99% CI: -1.3 to 13.4) vs. India 1.7 days (99% CI: -8.4 to 11.8)). For serious adverse reactions, the direction was reversed (RD for Europe -1.0% (99% CI: -7.1 to 5.2) vs. India -5.3% (99% CI: -16.2 to 5.0).

Interpretation: Our analysis suggests higher dose dexamethasone may have less beneficial effects for patients in India as compared with those in Europe; however, the evidence is weak, and this could represent a chance finding.

Funding: None for this analysis. The COVID STEROID 2 trial was funded by The Novo Nordisk Foundation and supported by Rigshospitalet's Research Council.

Keywords: COVID-19; Developing countries; Randomised controlled trials; Steroids.

PubMed Disclaimer

Conflict of interest statement

The Department of Intensive Care at Copenhagen University Hospital—Rigshospitalet has received funding for other projects from The Novo Nordisk Foundation, Pfizer, Sygeforsikringen “danmark”, and Fresenius Kabi, and conducts contract research for AM-Pharma. AG reports receiving support from Sygesforsikringen “danmark” for work unrelated to this manuscript. VJ reports consulting fees from Astra Zeneca, GSK, Zydus Life Sciences and Baxter Healthcare, all of which was paid to the Organization he works for. AP reports receiving consulting fees from Novartis for advisory board work.

Figures

Fig. 1
Fig. 1
Forest plot of categorical outcomes between Europe and India for the 12 mg vs. 6 mg Dexamethasone comparison.
Fig. 2
Fig. 2
Forest plot of continuous outcomes between Europe and India for the Dexamethasone 12 mg vs. 6 mg comparison.
Fig. 3
Fig. 3
Mortality at Day 180–Europe vs. India. Abbreviations: EU: Europe, IN: India.
See this image and copyright information in PMC

References

    1. The RECOVERY Collaborative Group Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384:693–704. - PMC - PubMed
    1. The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. 2020;324(13):1330–1341. - PMC - PubMed
    1. The COVID STEROID 2 Trial group Effect of 12mg vs. 6mg of dexamethasone on the number of days alive without life support in adults with COVID-19 and severe hypoxemia. JAMA. 2021;326(18):1807–1817. - PMC - PubMed
    1. Granholm A., Munch M.W., Myatra S.N., et al. Dexamethasone 12mg versus 6mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID-STEROID 2 trial. Intensive Care Med. 2022;48(1):45–55. - PMC - PubMed
    1. Granholm A., Kjaer M.N., Wunch M.W., et al. Long-term outcomes of dexamethasone 12mg versus 6mg in patients with COVID-19 and severe hypoxaemia. Intensive Care Med. 2022;48(5):580–589. - PMC - PubMed