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

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

doi:10.1007/s00134-022-06677-2

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Purpose: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference − 4.3%; 99% confidence interval (CI) − 11.7–3.0; relative risk 0.89; 0.72–1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI − 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (− 3 to 10; P = 0.22). Conclusion: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.

Original language	English
Journal	Intensive Care Medicine
Volume	48
Issue number	5
Pages (from-to)	580-589
ISSN	0342-4642
DOIs	https://doi.org/10.1007/s00134-022-06677-2
Publication status	Published - May 2022

Keywords

Corticosteroids
COVID-19
Critical illness
Hypoxaemia
Mortality
Quality of life
Dexamethasone/administration & dosage
COVID-19/complications
Humans
Hypoxia/complications
Treatment Outcome
Dose-Response Relationship, Drug
Patient Acuity
Quality of Life
Adult
Surveys and Questionnaires

Documents & Links

10.1007/s00134-022-06677-2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970069/pdf/134_2022_Article_6677.pdf

Cite this

Granholm, A., Kjær, M. B. N., Munch, M. W., Myatra, S. N., Vijayaraghavan, B. K. T., Cronhjort, M., Wahlin, R. R., Jakob, S. M., Cioccari, L., Vesterlund, G. K., Meyhoff, T. S., Helleberg, M., Møller, M. H., Benfield, T., Venkatesh, B., Hammond, N. E., Micallef, S., Bassi, A., John, O., ... Perner, A. (2022). Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia. Intensive Care Medicine, 48(5), 580-589. https://doi.org/10.1007/s00134-022-06677-2

@article{42add2bf19664bebb283fe190b988edb,

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

abstract = "Purpose: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference − 4.3%; 99% confidence interval (CI) − 11.7–3.0; relative risk 0.89; 0.72–1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI − 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (− 3 to 10; P = 0.22). Conclusion: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.",

keywords = "Corticosteroids, COVID-19, Critical illness, Hypoxaemia, Mortality, Quality of life, Dexamethasone/administration & dosage, COVID-19/complications, Humans, Hypoxia/complications, Treatment Outcome, Dose-Response Relationship, Drug, Patient Acuity, Quality of Life, Adult, Surveys and Questionnaires",

author = "Anders Granholm and Kj{\ae}r, {Maj Brit N{\o}rregaard} and Munch, {Marie Warrer} and Myatra, {Sheila Nainan} and Vijayaraghavan, {Bharath Kumar Tirupakuzhi} and Maria Cronhjort and Wahlin, {Rebecka Rubenson} and Jakob, {Stephan M.} and Luca Cioccari and Vesterlund, {Gitte Kingo} and Meyhoff, {Tine Sylvest} and Marie Helleberg and M{\o}ller, {Morten Hylander} and Thomas Benfield and Balasubramanian Venkatesh and Hammond, {Naomi E.} and Sharon Micallef and Abhinav Bassi and Oommen John and Vivekanand Jha and Kristiansen, {Klaus Tjelle} and Ulrik, {Charlotte Suppli} and J{\o}rgensen, {Vibeke Lind} and Margit Smitt and Bestle, {Morten H.} and Andreasen, {Anne Sofie} and Poulsen, {Lone Musaeus} and Rasmussen, {Bodil Steen} and Br{\o}chner, {Anne Craveiro} and Thomas Str{\o}m and Anders M{\o}ller and Khan, {Mohd Saif} and Ajay Padmanaban and Divatia, {Jigeeshu Vasishtha} and Sanjith Saseedharan and Kapil Borawake and Farhad Kapadia and Subhal Dixit and Rajesh Chawla and Urvi Shukla and Pravin Amin and Chew, {Michelle S.} and Wamberg, {Christian Aage} and Neeta Bose and Shah, {Mehul S.} and Darfelt, {Iben S.} and Christian Gluud and Theis Lange and Anders Perner",

note = "Funding Information: The Novo Nordisk Foundation and the Research Council of Rigshospitalet, Grant nos [0062998, E-22703-06]. The funders had no role in the design, conduct, analyses or reporting of the trial. Funding Information: AG, MBNK, MWM, GKV, TSM, MHM and AP are affiliated with the Dept. of Intensive Care, Rigshospitalet, which has received grants for research from Pfizer, Fresenius Kabi, AM Pharma, and Sygeforsikringen {\textquoteleft}danmark{\textquoteright} outside the submitted work. MH has participated in advisory boards for AstraZeneca, GSK, Gilead, MSD, Roche and Sobi and received speaker{\textquoteright}s honoraria from GSK and Gilead. TB reports grants from Novo Nordisk Foundation, grants from Simonsen Foundation, grants and personal fees from GSK, grants and personal fees from Pfizer, personal fees from Astra Zeneca, personal fees from Janssen, personal fees from Boehringer Ingelheim, grants and personal fees from Gilead, personal fees from MSD, grants from Lundbeck Foundation, grants from Kai Hansen Foundation, personal fees from Pentabase ApS, grants from Erik and Susanna Olesen{\textquoteright}s Charitable Fund, outside the submitted work. SMJ and LC are affiliated with Inselspital, Bern University Hospital, which has received grants from Edwards Lifesciences Services GmbH, Phagenesis Limited, and Nestl{\'e} outside the submitted work. JVD has received personal fees (paid to his institution) from Edwards India outside the submitted work. VJ has received grant funding from GSK, Baxter Healthcare, and Biocon and honoraria from Boehringer Ingelheim, Astra Zeneca, Baxter Healthcare, Bayer, NephroPlus and Zydus Cadilla, under the policy of all monies being paid to the organization. Publisher Copyright: {\textcopyright} 2022, Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2022",

month = may,

doi = "10.1007/s00134-022-06677-2",

language = "English",

volume = "48",

pages = "580--589",

journal = "Intensive Care Medicine",

issn = "0342-4642",

publisher = "Heinemann",

number = "5",

}

Granholm, A, Kjær, MBN, Munch, MW, Myatra, SN, Vijayaraghavan, BKT, Cronhjort, M, Wahlin, RR, Jakob, SM, Cioccari, L, Vesterlund, GK, Meyhoff, TS, Helleberg, M, Møller, MH, Benfield, T, Venkatesh, B, Hammond, NE, Micallef, S, Bassi, A, John, O, Jha, V, Kristiansen, KT, Ulrik, CS, Jørgensen, VL, Smitt, M, Bestle, MH, Andreasen, AS, Poulsen, LM, Rasmussen, BS, Brøchner, AC , Strøm, T, Møller, A, Khan, MS, Padmanaban, A, Divatia, JV, Saseedharan, S, Borawake, K, Kapadia, F, Dixit, S, Chawla, R, Shukla, U, Amin, P, Chew, MS, Wamberg, CA, Bose, N, Shah, MS, Darfelt, IS, Gluud, C, Lange, T & Perner, A 2022, 'Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia', Intensive Care Medicine, vol. 48, no. 5, pp. 580-589. https://doi.org/10.1007/s00134-022-06677-2

TY - JOUR

T1 - Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia

AU - Granholm, Anders

AU - Kjær, Maj Brit Nørregaard

AU - Munch, Marie Warrer

AU - Myatra, Sheila Nainan

AU - Vijayaraghavan, Bharath Kumar Tirupakuzhi

AU - Cronhjort, Maria

AU - Wahlin, Rebecka Rubenson

AU - Jakob, Stephan M.

AU - Cioccari, Luca

AU - Vesterlund, Gitte Kingo

AU - Meyhoff, Tine Sylvest

AU - Helleberg, Marie

AU - Møller, Morten Hylander

AU - Benfield, Thomas

AU - Venkatesh, Balasubramanian

AU - Hammond, Naomi E.

AU - Micallef, Sharon

AU - Bassi, Abhinav

AU - John, Oommen

AU - Jha, Vivekanand

AU - Kristiansen, Klaus Tjelle

AU - Ulrik, Charlotte Suppli

AU - Jørgensen, Vibeke Lind

AU - Smitt, Margit

AU - Bestle, Morten H.

AU - Andreasen, Anne Sofie

AU - Poulsen, Lone Musaeus

AU - Rasmussen, Bodil Steen

AU - Brøchner, Anne Craveiro

AU - Strøm, Thomas

AU - Møller, Anders

AU - Khan, Mohd Saif

AU - Padmanaban, Ajay

AU - Divatia, Jigeeshu Vasishtha

AU - Saseedharan, Sanjith

AU - Borawake, Kapil

AU - Kapadia, Farhad

AU - Dixit, Subhal

AU - Chawla, Rajesh

AU - Shukla, Urvi

AU - Amin, Pravin

AU - Chew, Michelle S.

AU - Wamberg, Christian Aage

AU - Bose, Neeta

AU - Shah, Mehul S.

AU - Darfelt, Iben S.

AU - Gluud, Christian

AU - Lange, Theis

AU - Perner, Anders

N1 - Funding Information: The Novo Nordisk Foundation and the Research Council of Rigshospitalet, Grant nos [0062998, E-22703-06]. The funders had no role in the design, conduct, analyses or reporting of the trial. Funding Information: AG, MBNK, MWM, GKV, TSM, MHM and AP are affiliated with the Dept. of Intensive Care, Rigshospitalet, which has received grants for research from Pfizer, Fresenius Kabi, AM Pharma, and Sygeforsikringen ‘danmark’ outside the submitted work. MH has participated in advisory boards for AstraZeneca, GSK, Gilead, MSD, Roche and Sobi and received speaker’s honoraria from GSK and Gilead. TB reports grants from Novo Nordisk Foundation, grants from Simonsen Foundation, grants and personal fees from GSK, grants and personal fees from Pfizer, personal fees from Astra Zeneca, personal fees from Janssen, personal fees from Boehringer Ingelheim, grants and personal fees from Gilead, personal fees from MSD, grants from Lundbeck Foundation, grants from Kai Hansen Foundation, personal fees from Pentabase ApS, grants from Erik and Susanna Olesen’s Charitable Fund, outside the submitted work. SMJ and LC are affiliated with Inselspital, Bern University Hospital, which has received grants from Edwards Lifesciences Services GmbH, Phagenesis Limited, and Nestlé outside the submitted work. JVD has received personal fees (paid to his institution) from Edwards India outside the submitted work. VJ has received grant funding from GSK, Baxter Healthcare, and Biocon and honoraria from Boehringer Ingelheim, Astra Zeneca, Baxter Healthcare, Bayer, NephroPlus and Zydus Cadilla, under the policy of all monies being paid to the organization. Publisher Copyright: © 2022, Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2022/5

Y1 - 2022/5

N2 - Purpose: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference − 4.3%; 99% confidence interval (CI) − 11.7–3.0; relative risk 0.89; 0.72–1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI − 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (− 3 to 10; P = 0.22). Conclusion: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.

AB - Purpose: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference − 4.3%; 99% confidence interval (CI) − 11.7–3.0; relative risk 0.89; 0.72–1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI − 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (− 3 to 10; P = 0.22). Conclusion: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.

KW - Corticosteroids

KW - COVID-19

KW - Critical illness

KW - Hypoxaemia

KW - Mortality

KW - Quality of life

KW - Dexamethasone/administration & dosage

KW - COVID-19/complications

KW - Humans

KW - Hypoxia/complications

KW - Treatment Outcome

KW - Dose-Response Relationship, Drug

KW - Patient Acuity

KW - Quality of Life

KW - Adult

KW - Surveys and Questionnaires

U2 - 10.1007/s00134-022-06677-2

DO - 10.1007/s00134-022-06677-2

M3 - Journal article

C2 - 35359168

AN - SCOPUS:85127422999

VL - 48

SP - 580

EP - 589

JO - Intensive Care Medicine

JF - Intensive Care Medicine

SN - 0342-4642

IS - 5

ER -

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

Abstract

Keywords

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