The University of Southampton
University of Southampton Institutional Repository

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

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
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 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.

Dexamethasone, Double-Blind Method, Drug Therapy, Combination, Glucocorticoids, Humans, Influenza, Human, Pandemics, Research Design, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
1366-5278
1-78, vii-viii
Lim, Wei Shen
89d4ce8c-fbc7-4f56-940e-e4c6533af05d
Brittain, Clare
b895c95c-1669-447a-af65-b8baab403eaa
Duley, Lelia
db76a61c-94d8-4ec8-82cd-d7baca16f665
Edwards, Sheila
87cae1ed-593b-4a9f-8ed8-5189dbb02ad2
Gordon, Stephen
da85e1a0-95f0-4b1a-9a11-c3519e5f1126
Montgomery, Alan
6f6e4e9e-e78b-43b0-9334-05522cfd6cdf
Nguyen-Van-Tam, Jonathan
ff14ae25-f3a5-42ed-8c0b-9dc3fac75638
Read, Robert
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Whitham, Diane
683ed54e-283e-47e0-98e3-fb02831fc862
Whynes, David
9cf8c269-7497-4052-98af-6431c6972a94
Woodhead, Mark
84f38357-4189-4f66-96b3-1a1e3a9a4b59
Wootton, Dan
5c4cfe62-a461-4a73-8571-8735829ffecf
Lim, Wei Shen
89d4ce8c-fbc7-4f56-940e-e4c6533af05d
Brittain, Clare
b895c95c-1669-447a-af65-b8baab403eaa
Duley, Lelia
db76a61c-94d8-4ec8-82cd-d7baca16f665
Edwards, Sheila
87cae1ed-593b-4a9f-8ed8-5189dbb02ad2
Gordon, Stephen
da85e1a0-95f0-4b1a-9a11-c3519e5f1126
Montgomery, Alan
6f6e4e9e-e78b-43b0-9334-05522cfd6cdf
Nguyen-Van-Tam, Jonathan
ff14ae25-f3a5-42ed-8c0b-9dc3fac75638
Read, Robert
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Whitham, Diane
683ed54e-283e-47e0-98e3-fb02831fc862
Whynes, David
9cf8c269-7497-4052-98af-6431c6972a94
Woodhead, Mark
84f38357-4189-4f66-96b3-1a1e3a9a4b59
Wootton, Dan
5c4cfe62-a461-4a73-8571-8735829ffecf

Lim, Wei Shen, Brittain, Clare, Duley, Lelia, Edwards, Sheila, Gordon, Stephen, Montgomery, Alan, Nguyen-Van-Tam, Jonathan, Read, Robert, Whitham, Diane, Whynes, David, Woodhead, Mark and Wootton, Dan (2015) 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, 19 (16), 1-78, vii-viii. (doi:10.3310/hta19160).

Record type: Article

Abstract

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.

Full text not available from this repository.

More information

Published date: February 2015
Keywords: Dexamethasone, Double-Blind Method, Drug Therapy, Combination, Glucocorticoids, Humans, Influenza, Human, Pandemics, Research Design, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416204
URI: https://eprints.soton.ac.uk/id/eprint/416204
ISSN: 1366-5278
PURE UUID: c60ca0f1-b026-43fa-8052-847c1a358ab3
ORCID for Robert Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 07 Dec 2017 17:30
Last modified: 14 Mar 2019 01:36

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×