Can oral corticosteroids reduce the severity or duration of an acute cough, and the associated National Health Service and societal costs, in adults presenting to primary care? Study protocol for a randomised controlled trial.

Harriet E Downing,On Behalf Of The Osac Trial Team ,Sandra Hollinghurst,Anthony Harnden,Sara T Brookes,Margaret T May,David Timmins,Paul Little,Alastair D Hay,Matthew Thompson,Mike V Moore,Elizabeth Orton,Fran Carroll,Kay Wang,Denise Kendrick

doi:10.1186/s13063-015-0569-5

Abstract

BackgroundAcute lower respiratory tract infection (LRTI) is one of the most common conditions managed internationally and is costly to health services and patients. Despite good evidence that antibiotics are not effective for improving the symptoms of uncomplicated LRTI, they are widely prescribed, contributing to antimicrobial resistance. Many of the symptoms observed in LRTI are mediated by inflammatory processes also observed in exacerbations of asthma, for which there is strong evidence of corticosteroid effectiveness. The primary aim of the OSAC (Oral Steroids for Acute Cough) Trial is to determine whether oral prednisolone (40 mg daily for 5 days) can reduce the duration of moderately bad (or worse) cough and the severity of all its associated symptoms on days 2 to 4 post-randomisation (day 1 is trial entry) by at least 20% in adults ≥18 years with acute LRTI presenting to primary care.Methods/designOSAC is a two-arm, multi-centre, placebo-controlled, randomised superiority trial. The target sample size is 436 patients, which allows for a 20% dropout rate. Patients will be recruited from primary care sites (General Practitioner surgeries) across England and followed up until symptom resolution. The two primary clinical outcomes are the duration of moderately bad (or worse) cough, and the severity of all its associated symptoms on days 2 to 4 post-randomisation. Secondary outcomes include: antibiotic consumption; symptom burden; adverse events; participant satisfaction with treatment and intention to consult for future similar illnesses. A parallel economic evaluation will investigate the cost-effectiveness of the intervention.DiscussionResults from the OSAC trial will increase knowledge regarding the clinical and cost-effectiveness of corticosteroids for LRTI, and will establish the potential of a new treatment option that could substantially improve patient health. We have chosen a relatively high ‘efficacy dose’ as this will enable us to decide on the potential for further research into lower dose oral and/or inhaled corticosteroids. This trial will also contribute to a growing body of research investigating the natural course of this very common illness, as well as the effects of steroids on the undesirable inflammatory symptoms associated with infection.Trial registrationCurrent Controlled Trials ISRCTN57309858 (31 January 2013).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0569-5) contains supplementary material, which is available to authorized users.

Highlights

Acute lower respiratory tract infection (LRTI) is one of the most common conditions managed internationally and is costly to health services and patients
We have chosen a relatively high ‘efficacy dose’ as this will enable us to decide on the potential for further research into lower dose oral and/or inhaled corticosteroids
Eligibility We wish to test the effects of corticosteroids in adults presenting to primary care with acute LRTI, in whom there is no evidence of pneumonia or other reason to require an immediate antibiotic or hospitalisation, and in whom there is no reason to consider the use of oral prednisolone 40 mg daily for 5 days unsafe

Summary

Discussion

This paper describes a placebo-controlled, randomised multi-centre superiority trial that will establish the clinical and cost effectiveness of a commonly used treatment (corticosteroids) for an entirely novel indication and one of the commonest clinical problems managed in primary care: acute LRTI. MVM and AH contributed to the development of the research question and the trial design and, as Principal Investigators, supervised the implementation of the trial protocol in the Southampton and Oxford centres, respectively. DK contributed to the development of the research question and the trial design, supervised the implementation of the trial protocol in the Nottingham centre as Principal Investigator, and contributed to the drafting of the manuscript. FC, the trial Health Economics Research Associate, contributed to the Health Economics Analysis Plan and to the drafting of the manuscript. EO contributed to the trial design, to the supervision of trial implementation in the Nottingham centre, and to the drafting of the manuscript. KW contributed to the trial design, to the supervision of trial implementation in the Oxford centre, and to the drafting of the manuscript. All authors listed provided critical review and final approval of the manuscript

Background

Findings