Oral Steroids for Acute Cough (OSAC): a multi-centre, placebo controlled, randomised trial
The majority of UK adults experience at least one lower respiratory tract infection (LRTI) a year, costing the NHS around £190m annually. Over 75% of adults consulting primary care receive antibiotics, exacerbating antimicrobial resistance, without substantial clinical benefit. Many LRTI symptoms overlap with those of acute asthma, for which inhaled and oral corticosteroids are known to be effective. Despite an absence of evidence, GPs are using inhaled and oral corticosteroids in some LRTI patients. OSAC seeks to demonstrate ‘proof of concept' symptomatic effectiveness and cost-effectiveness of a moderate dose oral corticosteroid for adults with acute LRTI.
OSAC was a placebo RCT of 40mg prednisolone daily for 5 days. Eligible patients were: 18 years or older; presenting with an acute (?28 days) cough with at least one of phlegm, chest pain, wheezing or shortness of breath; and the attending clinician willing to use a ‘delayed' or ‘no antibiotic' prescribing strategy. Patients with: known asthma, COPD or lung cancer; requiring same-day antibiotics; or with prednisolone contraindications were excluded.Participants completed a symptom diary for at least 7 days, and up to 28 days, to measure two primary outcomes: the duration of moderately bad (or worse) cough; and the average severity of all symptoms on days 2 to 4 (including cough, phlegm, shortness of breath, disturbed sleep, feeling generally unwell and interference with normal activities/work). Resource use data were collected using the same method. Outcome data were required for 348 participants to demonstrate the minimum clinically important (20%) reduction in each primary outcome, with at least 90% power and two-sided alpha of 5%. Assuming 20% attrition, we aimed to recruit 436 participants.
Between July 2013 and October 2014, 397 participants were recruited to the two trial arms (in a ratio of 198:199) from 53 GP practices across four centres (Bristol, Southampton, Nottingham & Oxford). Primary outcome attrition rates were lower than expected: moderately bad (or worse) cough duration was available for 357 (89%), and symptom severity for 371 (94%) of participants. The primary analysis is currently in progress and will be presented at the conference.
To our knowledge, OSAC is the first trial of oral corticosteroids for community resident adults with acute LRTI. If results are positive, we think future research should investigate the clinical and cost-effectiveness of lower dose oral or inhaled corticosteroids for acute LRTI, as a potential alternative treatment option in the drive to reduce unnecessary antibiotic prescribing. In addition, clinicians might reasonably prescribe oral prednisolone for patients willing to accept the benefits and risks of moderate dose oral corticosteroids. If results are negative, then we believe low dose oral or inhaled corticosteroids are unlikely to be effective, obviating the need for further research.
- Alastair Hay, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Harriet Downing, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Sara Brookes, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Anthony Harnden, Division of Primary Care, University of Nottingham, Nottingham, UK
- Sandra Hollinghurst, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Denise Kendrick, Faculty of Medicine, University of Southampton, Southampton, UK
- Paul Little
- Margaret May, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Michael Moore
- Elizabeth Orton, Faculty of Medicine, University of Southampton, Southampton, UK
- Matthew Thompson, Division of Primary Care, University of Nottingham, Nottingham, UK
- Kay Wang, Division of Primary Care, University of Nottingham, Nottingham, UK