Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial ‘in hibernation’, ready for rapid activation
Background: There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in infl...
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NIHR Journals Library
2015-02-01
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Series: | Health Technology Assessment |
Online Access: | https://doi.org/10.3310/hta19160 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Shen Lim Clare Brittain Lelia Duley Sheila Edwards Stephen Gordon Alan Montgomery Jonathan Nguyen-Van-Tam Robert Read Diane Whitham David Whynes Mark Woodhead Dan Wootton |
spellingShingle |
Wei Shen Lim Clare Brittain Lelia Duley Sheila Edwards Stephen Gordon Alan Montgomery Jonathan Nguyen-Van-Tam Robert Read Diane Whitham David Whynes Mark Woodhead Dan Wootton Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial ‘in hibernation’, ready for rapid activation Health Technology Assessment |
author_facet |
Wei Shen Lim Clare Brittain Lelia Duley Sheila Edwards Stephen Gordon Alan Montgomery Jonathan Nguyen-Van-Tam Robert Read Diane Whitham David Whynes Mark Woodhead Dan Wootton |
author_sort |
Wei Shen Lim |
title |
Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial ‘in hibernation’, ready for rapid activation |
title_short |
Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial ‘in hibernation’, ready for rapid activation |
title_full |
Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial ‘in hibernation’, ready for rapid activation |
title_fullStr |
Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial ‘in hibernation’, ready for rapid activation |
title_full_unstemmed |
Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial ‘in hibernation’, ready for rapid activation |
title_sort |
blinded randomised controlled trial of low-dose adjuvant steroids in adults admitted to hospital with pandemic influenza (asap): a trial ‘in hibernation’, ready for rapid activation |
publisher |
NIHR Journals Library |
series |
Health Technology Assessment |
issn |
1366-5278 2046-4924 |
publishDate |
2015-02-01 |
description |
Background: There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias. Objectives: To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an ‘off-the-shelf’ clinical trial that is ready to be activated in a future pandemic. Design: Multicentre, pragmatic, blinded, randomised placebo-controlled trial. Setting: Thirty to 40 hospitals in the UK. Participants: Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic. Intervention: Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission. Main outcome measure: Admission to Intensive Care Unit, or death, within 30 days of admission to hospital. Results: This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified. Conclusions: This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other ‘off-the-shelf’ trials as part of preparedness planning for public health emergencies. Trial registration: Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013–001051–12. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information. |
url |
https://doi.org/10.3310/hta19160 |
work_keys_str_mv |
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doaj-a4468b9c324e4adcbb17069308e94dd42020-11-24T21:47:41ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242015-02-01191610.3310/hta1916011/46/01Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial ‘in hibernation’, ready for rapid activationWei Shen Lim0Clare Brittain1Lelia Duley2Sheila Edwards3Stephen Gordon4Alan Montgomery5Jonathan Nguyen-Van-Tam6Robert Read7Diane Whitham8David Whynes9Mark Woodhead10Dan Wootton11Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UKNottingham Clinical Trials Unit, University of Nottingham, Nottingham, UKNottingham Clinical Trials Unit, University of Nottingham, Nottingham, UKBritish Thoracic Society, London, UKSchool of Tropical Medicine, Liverpool School of Tropical Medicine, Liverpool, UKNottingham Clinical Trials Unit, University of Nottingham, Nottingham, UKDivision of Epidemiology and Public Health, University of Nottingham, Nottingham, UKFaculty of Medicine, University of Southampton, Southampton, UKNottingham Clinical Trials Unit, University of Nottingham, Nottingham, UKSchool of Economics, University of Nottingham, Nottingham, UKRespiratory Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UKInstitute of Infection and Global Health, University of Liverpool, Liverpool, UKBackground: There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias. Objectives: To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an ‘off-the-shelf’ clinical trial that is ready to be activated in a future pandemic. Design: Multicentre, pragmatic, blinded, randomised placebo-controlled trial. Setting: Thirty to 40 hospitals in the UK. Participants: Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic. Intervention: Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission. Main outcome measure: Admission to Intensive Care Unit, or death, within 30 days of admission to hospital. Results: This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified. Conclusions: This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other ‘off-the-shelf’ trials as part of preparedness planning for public health emergencies. Trial registration: Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013–001051–12. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.https://doi.org/10.3310/hta19160 |