title: 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.
abstract: BACKGROUND
  Acute 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
  OSAC 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.
  
  
  CONCLUSIONS
  Results 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.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN57309858 (31 January 2013).
authors.affiliation: Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol, BS8 2PS, UK. harriet.downing@bristol.ac.uk.
authors.forename: Harriet E
authors.initials: HE
authors.lastname: Downing
authors.affiliation: Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol, BS8 2PS, UK. fran.carroll@bristol.ac.uk.
authors.forename: Fran
authors.initials: F
authors.lastname: Carroll
authors.affiliation: Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol, BS8 2PS, UK. s.t.brookes@bristol.ac.uk.
authors.forename: Sara T
authors.initials: ST
authors.lastname: Brookes
authors.affiliation: Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol, BS8 2PS, UK. s.p.hollinghurst@bristol.ac.uk.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hollinghurst
authors.affiliation: Nuffield Department of Primary Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK. david.timmins@phc.ox.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Timmins
authors.affiliation: Division of Primary Care, University of Nottingham, Floor 13, Tower Building, University Park, Nottingham, NG7 2RD, UK. elizabeth.orton@nottingham.ac.uk.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Orton
authors.affiliation: Nuffield Department of Primary Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK. kay.wang@phc.ox.ac.uk.
authors.forename: Kay
authors.initials: K
authors.lastname: Wang
authors.affiliation: Division of Primary Care, University of Nottingham, Floor 13, Tower Building, University Park, Nottingham, NG7 2RD, UK. denise.kendrick@nottingham.ac.uk.
authors.forename: Denise
authors.initials: D
authors.lastname: Kendrick
authors.affiliation: University of Southampton, Aldermoor Health Centre, Aldermoor Close, Southampton, SO15 5ST, UK. p.little@soton.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Little
authors.affiliation: University of Southampton, Aldermoor Health Centre, Aldermoor Close, Southampton, SO15 5ST, UK. mvm198@soton.ac.uk.
authors.forename: Mike V
authors.initials: MV
authors.lastname: Moore
authors.affiliation: Nuffield Department of Primary Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK. anthony.harnden@phc.ox.ac.uk.
authors.forename: Anthony
authors.initials: A
authors.lastname: Harnden
authors.affiliation: Nuffield Department of Primary Care Health Sciences, New Radcliffe House, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK. matthew.thompson@phc.ox.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol, BS8 2PS, UK. m.t.may@bristol.ac.uk.
authors.forename: Margaret T
authors.initials: MT
authors.lastname: May
authors.affiliation: Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol, BS8 2PS, UK. alastair.hay@bristol.ac.uk.
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Hay
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D002985:Clinical Protocols; D003371:Cough / Q000188:drug therapy*; D017048:Health Care Costs; D006801:Humans; D009313:National Health Programs; D017063:Outcome Assessment, Health Care; D011320:Primary Health Care; D012141:Respiratory Tract Infections / Q000188:drug therapy; D018401:Sample Size; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones