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Inhaled Budesonide in the Treatment of Early COVID-19 Illness: A Randomised Controlled Trial

25 Pages Posted: 8 Feb 2021

See all articles by Sanjay Ramakrishnan

Sanjay Ramakrishnan

University of Oxford - Nuffield Department of Clinical Medicine

Dan V. Nicolau

University of Oxford - Nuffield Department of Clinical Medicine

Beverly Langford

University of Oxford - Nuffield Department of Clinical Medicine

Mahdi Mahdi

University of Oxford - Nuffield Department of Clinical Medicine

Helen Jeffers

University of Oxford - Nuffield Department of Clinical Medicine

Christine Mwasuku

University of Oxford - Nuffield Department of Clinical Medicine

Karolina Krassowska

University of Oxford - Nuffield Department of Clinical Medicine

Ian Binnian

Eynsham Medical Group

Victoria Glover

White Horse Medical Practice

Stephen Bright

Windrush Medical Practice

Christopher Butler

University of Oxford - Nuffield Department of Primary Care Health Sciences

Jennifer L. Cane

University of Oxford - Nuffield Department of Clinical Medicine

Andreas Halner

University of Oxford - Nuffield Department of Clinical Medicine

Philippa C. Matthews

University of Oxford - Nuffield Department of Medicine; Government of the United Kingdom - Department of Infectious Diseases and Microbiology

Louise E. Donnelly

Imperial College London - National Heart and Lung Institute (NHLI)

Jodie L. Simpson

University of Newcastle (Australia) - Priority Research Centre for Healthy Lungs

Jonathan R. Baker

Imperial College London - National Heart and Lung Institute (NHLI)

Nabil T. Fadai

University of Nottingham

Stefan Peterson

StatMind

Thomas Bengtsson

StatMind

Peter J. Barnes

Imperial College London - National Heart and Lung Institute (NHLI)

Richard EK Russell

University of Oxford - Nuffield Department of Clinical Medicine

Mona Bafadhel

University of Oxford - Respiratory Medicine Unit

More...

Abstract

Background:  Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented.  We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. 

Methods: We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. 

Results: 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. 

Conclusion: Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.

Trial Registration: ClinicalTrials.gov number, NCT04416399

Funding: Oxford NIHR Biomedical Research Centre and AstraZeneca

Declaration of Interests: Dr. Ramakrishnan reports grants and non-financial support from Oxford Respiratory NIHR BRC, during the conduct of the study; non-financial support from AstraZeneca, personal fees from Australian Government Research Training Program, outside the submitted work; . Dr. Nicolau has nothing to disclose. Mrs Langford has nothing to disclose. Mr. Mahdi has nothing to disclose. Mrs Helen Jeffers reports personal fees from AstraZeneca, outside the submitted work; . Miss Mwasuku has nothing to disclose. Mrs Krassowska has nothing to disclose. Dr Fox has nothing to disclose. Dr Binnian has nothing to disclose. Dr Glover has nothing to disclose. Dr Bright has nothing to disclose. Dr. Butler reports grants from National Institute for Health Research (NIHR), Roche Molecular Diagnostics, Janssen Pharmaceuticals, and various public funding bodies for research related to diagnostics and infections. He has revcied personal fees from Pfizer INC, Roche Diagnostics, and Janssen Pharmaceuticals, outside the submitted work. Dr. Cane has nothing to disclose. Mr. Halner has nothing to disclose. Dr. Matthews has nothing to disclose. Dr. Donnelly reports grants from AstraZeneca, from Boehringer-Ingelheim, outside the submitted work; . Dr. Simpson has nothing to disclose. Dr Baker has nothing to disclose. Dr. Fadai has nothing to disclose. Dr. Peterson reports personal fees from AstraZeneca, outside the submitted work; . Mr. Bengtsson reports personal fees from AstraZeneca, outside the submitted work; Dr. Barnes reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Teva, personal fees from Covis, during the conduct of the study; Dr. Russell reports grants from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi UK, personal fees from Glaxo-SmithKline, during the conduct of the study; . Dr. Bafadhel reports grants from AstraZeneca, personal fees from AstraZeneca, Chiesi, GSK, other from Albus Health, ProAxsis, outside the submitted work; .

Ethics Approval Statement: The trial was sponsored by the University of Oxford, and was approved by the Fulham London Research Ethics Committee (20/HRA/2531) and the National Health Research Authority.The ethical approval number is 20/HRA/2531.

Suggested Citation

Ramakrishnan, Sanjay and Nicolau, Dan V. and Langford, Beverly and Mahdi, Mahdi and Jeffers, Helen and Mwasuku, Christine and Krassowska, Karolina and Binnian, Ian and Glover, Victoria and Bright, Stephen and Butler, Christopher and Cane, Jennifer L. and Halner, Andreas and Matthews, Philippa C. and Donnelly, Louise E. and Simpson, Jodie L. and Baker, Jonathan R. and Fadai, Nabil T. and Peterson, Stefan and Bengtsson, Thomas and Barnes, Peter J. and Russell, Richard EK and Bafadhel, Mona, Inhaled Budesonide in the Treatment of Early COVID-19 Illness: A Randomised Controlled Trial. Available at SSRN: https://ssrn.com/abstract=3777194 or http://dx.doi.org/10.2139/ssrn.3777194

Sanjay Ramakrishnan

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Dan V. Nicolau

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Beverly Langford

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Mahdi Mahdi

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Helen Jeffers

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Christine Mwasuku

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Karolina Krassowska

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Ian Binnian

Eynsham Medical Group ( email )

United Kingdom

Victoria Glover

White Horse Medical Practice ( email )

Faringdon
United Kingdom

Stephen Bright

Windrush Medical Practice ( email )

Witney
United Kingdom

Christopher Butler

University of Oxford - Nuffield Department of Primary Care Health Sciences ( email )

Oxford
United Kingdom

Jennifer L. Cane

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Andreas Halner

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Philippa C. Matthews

University of Oxford - Nuffield Department of Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Government of the United Kingdom - Department of Infectious Diseases and Microbiology ( email )

United Kingdom

Louise E. Donnelly

Imperial College London - National Heart and Lung Institute (NHLI) ( email )

Emmanuel Kaye Building
London, SW3 6LR
United Kingdom

Jodie L. Simpson

University of Newcastle (Australia) - Priority Research Centre for Healthy Lungs

Newcastle, NSW
Australia

Jonathan R. Baker

Imperial College London - National Heart and Lung Institute (NHLI) ( email )

Emmanuel Kaye Building
London, SW3 6LR
United Kingdom

Nabil T. Fadai

University of Nottingham

University Park
Nottingham, NG8 1BB
United Kingdom

Stefan Peterson

StatMind

Lund
Sweden

Thomas Bengtsson

StatMind ( email )

Lund
Sweden

Peter J. Barnes

Imperial College London - National Heart and Lung Institute (NHLI) ( email )

Emmanuel Kaye Building
London, SW3 6LR
United Kingdom

Richard EK Russell

University of Oxford - Nuffield Department of Clinical Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Mona Bafadhel (Contact Author)

University of Oxford - Respiratory Medicine Unit ( email )

Oxford
United Kingdom

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