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, Anders Granholm, Marie W. Munch, Maj Brit N. Kjær, Morten H. Møller, Anders Perner, Sheila N. Myatra, Vivekanand Jha, Vivekanand Jha, Vivekanand Jha, Naomi Hammond, Sharon Micallef, Balasubramanian Venkatesh, Naomi Hammond, Theis Lange, Marie W. Munch, Sheila N. Myatra, Bharath Kumar Tirupakuzhi Vijayaraghavan, Sanjith Saseedharan, Thomas BenfieldRebecka R. Wahlin, Bodil S. Rasmussen, Anne Sofie Andreasen, Lone M. Poulsen, Luca Cioccari, Mohd S. Khan, Farhad Kapadia, Jigeeshu V. Divatia, Anne C. Brøchner, Morten H. Bestle, Marie Helleberg, Jens Michelsen, Ajay Padmanaban, Neeta Bose, Anders Møller, Kapil Borawake, Klaus T. Kristiansen, Urvi Shukla, Michelle S. Chew, Charlotte S. Ulrik, Maj Brit N. Kjær, Morten H. Møller, Tine S. Meyhoff, Gitte K. Vesterlund, Christian Gluud, Theis Lange, Klaus V. Marcussen, Henrik Nielsen, Thomas S. Jensen, Anders Perner, the COVID-STEROID 2 collaborators

Research output: Contribution to journalJournal articleResearchpeer-review

10 Downloads (Pure)

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.

Original languageEnglish
Article number100293
JournalThe Lancet Regional Health - Southeast Asia
Volume20
Number of pages8
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Keywords

  • COVID-19
  • Developing countries
  • Randomised controlled trials
  • Steroids

Cite this