Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia

Granholm, Anders; Kjær, Maj-Brit Nørregaard; Munch, Marie Warrer; Myatra, Sheila Nainan; Vijayaraghavan, Bharath Kumar Tirupakuzhi; Cronhjort, Maria; Wahlin, Rebecka Rubenson; Jakob, Stephan M.; Cioccari, Luca; Vesterlund, Gitte Kingo; Meyhoff, Tine Sylvest; Helleberg, Marie; Møller, Morten Hylander; Benfield, Thomas; Venkatesh, Balasubramanian; Hammond, Naomi; Micallef, Sharon; Bassi, Abhinav; John, Oommen; Jha, Vivekanand; Kristiansen, Klaus Tjelle; Ulrik, Charlotte Suppli; Jørgensen, Vibeke Lind; Smitt, Margit; Bestle, Morten H.; Andreasen, Anne Sofie; Poulsen, Lone Musaeus; Rasmussen, Bodil Steen; Brøchner, Anne Craveiro; Strøm, Thomas; Møller, Anders; Khan, Mohd Saif; Padmanaban, Ajay; Divatia, Jigeeshu Vasishtha; Saseedharan, Sanjith; Borawake, Kapil; Kapadia, Farhad; Dixit, Subhal; Chawla, Rajesh; Shukla, Urvi; Amin, Pravin; Chew, Michelle; Wamberg, Christian; Bose, Neeta; Shah, Mehul; Darfelt, Iben S.; Gluud, Christian; Lange, Theis; Perner, Anders

doi:10.1007/s00134-022-06677-2

Cited by 21 publications

(36 citation statements)

References 21 publications

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“…The COVID STEROID 2 trial was an investigator-initiated, international, parallel-group, blinded randomised clinical trial). (3-5) Detailed descriptions of the trial methods, interventions, outcomes, statistical analyses, and the results for the COVID STEROID 2 trial have been published elsewhere. (3-5) In brief, 1000 adult patients hospitalised with COVID-19 and severe hypoxaemia (requiring ≥10 L oxygen/minute or mechanical ventilation) were enrolled from 31 sites in 26 hospitals in Denmark, India, Sweden and Switzerland between 27 August 2020 and 20 May 2021.…”

Section: Methodsmentioning

confidence: 99%

“…(3-5) Detailed descriptions of the trial methods, interventions, outcomes, statistical analyses, and the results for the COVID STEROID 2 trial have been published elsewhere. (3-5) In brief, 1000 adult patients hospitalised with COVID-19 and severe hypoxaemia (requiring ≥10 L oxygen/minute or mechanical ventilation) were enrolled from 31 sites in 26 hospitals in Denmark, India, Sweden and Switzerland between 27 August 2020 and 20 May 2021. Patients were randomised 1:1 to dexamethasone 12 mg or 6 mg intravenously (IV) once daily for up to 10 days.…”

Section: Methodsmentioning

confidence: 99%

“…(1,2) In the international COVID STEROID 2 randomised trial (n=1000) comparing higher (12 mg) vs lower doses (6 mg) of dexamethasone for patients with COVID-19 and severe hypoxaemia, there was a high probability of benefit from the higher dose for all outcomes assessed up until day 90. (3,4) Long-term outcomes were similarly mostly compatible with benefit (5) Of the analysed trial population, 613 patients were enrolled in Europe (Denmark, Sweden, and Switzerland) and 369 patients in India. There was a suggestion of heterogeneity of treatment effect (HTE) on the primary outcome (days alive without life support at 28 days) when comparing the subgroup of patients enrolled in Europe vs. India [adjusted mean difference (MD) in Europe: 1.8 days (95% confidence interval (CI) 0.2 to 3.4 days) vs India: 0.5 days (95% CI: -1.7 to 2.6)]; however, this was not statistically significant (test of interaction P = 0.57).…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneity of treatment effect of higher dose dexamethasone by geographic region in patients with COVID-19 and severe hypoxemia - Apost hocevaluation of the COVID STEROID 2 trial

Vijayaraghavan

Granholm

Myatra

et al. 2022

Preprint

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Background: The COVID-STEROID 2 trial found high probability of benefit with dexamethasone 12 mg vs. 6 mg daily among patients with COVID-19 and severe hypoxemia. There was suggestion of heterogeneity of treatment effects (HTE)between patients enrolled from Europe vs. India on the primary outcome. Whether there was HTE by geographical region for the remaining prespecified patient-important outcomes is unclear. Methods: We evaluated HTE by geographical region (Europe vs. India) for all secondary outcomes assessed in the trial with analyses adjusted for stratification variables. The results are presented as risk differences (RDs) or mean differences (MDs) with 99% confidence intervals (CIs) and P-values from interaction tests. Results: We found HTE for mortality at day 28 (RD for Europe -8.3% (99 % CI: -17.7 to 1.0) vs. RD for 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. RD for 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. RD for 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. MD for India 1.7 days (99% CI:-8.4 to11.8)). For serious adverse reactions, the direction was reversed (RD for Europe -1.0% (99% CI:-7.1 to 5.2) vs. RD for India -5.3% (99% CI: -16.2 to 5.0). For HRQoL outcomes, MD in EQ-5D-5L index values was 0.08(99%CI: -0.01 to 0.16) for Europe and 0.02(99%CI:-0.10 to 0.14) for India. For EQ VAS, MD was 4.4(95%CI:-3.1 to 11.9) for Europe and 2.6(99%CI:-9.0 to 14.2) for India. P values for all tests of interaction were ≥0.12. Conclusions: In this post hoc exploratory analysis, we found that higher dose dexamethasone may have lower beneficial effects for patients in India as compared with those in Europe without an increase in serious adverse reactions.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heterogeneity of treatment effect of higher dose dexamethasone by geographic region in patients with COVID-19 and severe hypoxemia - Apost hocevaluation of the COVID STEROID 2 trial

Vijayaraghavan

Granholm

Myatra

et al. 2022

Preprint

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“…A recent multinational randomised controlled trial found that 12 mg dexamethasone may be more beneficial than the typically employed 6 mg dose. 10 …”

Section: The Changes In the Characteristics Of The Pandemic And In Ou...mentioning

confidence: 99%

“…The impact of adopting beneficial treatments identified by clinical trials needs to be examined in more detail, to determine, for example, the appropriate use of prone ventilation or the optimal steroid dose. A recent multinational randomised controlled trial found that 12 mg dexamethasone may be more beneficial than the typically employed 6 mg dose 10 …”

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confidence: 99%

How intensive care has adapted to the changing face of COVID ‐19 in Australia

Jacques

Deshpande

2022

Medical Journal of Australia

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Long-term outcomes of patients with COVID-19 treated with helmet noninvasive ventilation or usual respiratory support: follow-up study of the Helmet-COVID randomized clinical trial

et al. 2023

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Purpose To evaluate whether helmet noninvasive ventilation compared to usual respiratory support reduces 180-day mortality and improves health-related quality of life (HRQoL) in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Methods This is a pre-planned follow-up study of the Helmet-COVID trial. In this multicenter, randomized clinical trial, adults with acute hypoxemic respiratory failure ( n = 320) due to coronavirus disease 2019 (COVID-19) were randomized to receive helmet noninvasive ventilation or usual respiratory support. The modified intention-to-treat population consisted of all enrolled patients except three who were lost at follow-up. The study outcomes were 180-day mortality, EuroQoL (EQ)-5D-5L index values, and EQ-visual analog scale (EQ-VAS). In the modified intention-to-treat analysis, non-survivors were assigned a value of 0 for EQ-5D-5L and EQ-VAS. Results Within 180 days, 63/159 patients (39.6%) died in the helmet noninvasive ventilation group compared to 65/158 patients (41.1%) in the usual respiratory support group (risk difference − 1.5% (95% confidence interval [CI] − 12.3, 9.3, p = 0.78). In the modified intention-to-treat analysis, patients in the helmet noninvasive ventilation and the usual respiratory support groups did not differ in EQ-5D-5L index values (median 0.68 [IQR 0.00, 1.00], compared to 0.67 [IQR 0.00, 1.00], median difference 0.00 [95% CI − 0.32, 0.32; p = 0.91]) or EQ-VAS scores (median 70 [IQR 0, 93], compared to 70 [IQR 0, 90], median difference 0.00 (95% CI − 31.92, 31.92; p = 0.55). Conclusions Helmet noninvasive ventilation did not reduce 180-day mortality or improve HRQoL compared to usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-023-06981-5.

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Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia

Cited by 21 publications

References 21 publications

Heterogeneity of treatment effect of higher dose dexamethasone by geographic region in patients with COVID-19 and severe hypoxemia - Apost hocevaluation of the COVID STEROID 2 trial

Heterogeneity of treatment effect of higher dose dexamethasone by geographic region in patients with COVID-19 and severe hypoxemia - Apost hocevaluation of the COVID STEROID 2 trial

How intensive care has adapted to the changing face of COVID ‐19 in Australia

Long-term outcomes of patients with COVID-19 treated with helmet noninvasive ventilation or usual respiratory support: follow-up study of the Helmet-COVID randomized clinical trial

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