Plain English Summary
Background and study aims
Most people get at least one chest infection every year and a high proportion present to health services and need to take time off work/other responsibilities. Symptoms are frequently prolonged (lasting 3 to 4 weeks) and no treatment (including antibiotics) has been shown to reduce either symptom severity or duration. Despite this, and strong evidence that inappropriate antibiotic prescribing fuels the development of the antibiotic-resistant bacterial strains (including MRSA), around 75% of adults presenting to GPs are still prescribed antibiotics. Many of the symptoms of chest infections (cough, phlegm, shortness of breath and wheeze) overlap with those of asthma attacks. While there is good evidence that steroids help patients with asthma, very little research has been conducted to assess if steroids can have the same beneficial effects in non-asthmatic patients suffering from chest infections. More evidence is needed to help doctors to understand if a high dose of steroids (given by tablets) are better than antibiotics, and could help doctors and patients to rely less on antibiotics. A high dose has been selected to maximise the chances of the study detecting an effect. If effects are found, lower doses will be tested in the future.
Who can participate?
Non-asthmatic adults with a chest infection.
What does the study involve?
Participants will be randomly given either a 5-day course of (active) steroid tablets or a 5-day course of placebo tablets that look, feel and taste identical to the steroid tablets but are inactive. We will ask them to complete a daily symptom diary for up to 4 weeks.
What are the possible benefits and risks of participating?
If the use of steroids was to reduce the annual cost of treating chest infections by as little as 1%, then the NHS would recoup the cost of the study in one year. Participation will not affect patients’ access to all other aspects of usual care and, in an emergency, their doctor will be able to find out which treatment they were given.
Where is the study run from?
University of Bristol (UK).
When is the study starting and how long is it expected to run for?
February 2013 to April 2014.
Who is funding the study?
National Institute for Health Research (NIHR) (UK).
Who is the main contact?
Mrs Harriet Downing
Department of Social Medicine
What is the clinical and cost effectiveness of oral steroids in the treatment of acute lower respiratory tract infection (LRTI)? A placebo controlled randomised trial
To test whether the use of oral prednisolone 40mg daily for 5 days will reduce the duration of moderately bad or worse cough, and its associated severity, by at least 20% when compared to no steroid treatment (usual care).
A two-arm, individually-randomised, placebo-controlled, blinded superiority trial comparing oral steroids with placebo in patients attending primary care with acute LRTI.
More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13751
Two-arm individually randomised placebo-controlled blinded superiority trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Acute lower respiratory tract infection
Oral prednisolone (40 mg daily) or matched placebo for up to five consecutive days
Primary outcome measures
Duration of moderately bad or worse cough (using a validated web/paper based symptom diary)
Secondary outcome measures
1. The mean of all symptom severity scores on days 2 to 4 (where day 1 is the day after the consultation day, measured using the symptom diary).
2. Antibiotic consumption (symptom diary)
3. Duration of steroid tablet use (symptom diary)
4. Total duration and severity of other symptoms (cough until very little problem; phlegm; wheeze; fever; chest pain; shortness of breath; sleep disturbance; activity disturbance; and feeling unwell) and abnormal peak flow (symptom diary)
5. Adverse events including reconsultation for a documented deterioration in illness or hospital admission (symptom diary and primary care notes review)
6. Patient satisfaction with treatment and intention to consult for future similar illnesses (symptom diary)
7. Clinical diagnosis of asthma at 3 months (primary care notes review)
8. Quality of life using the EQ-5D (as recommended by NICE, web/paper based questionnaire)
9. NHS treatment and investigation (e.g. chest x-rays, reconsultation) costs (primary care notes review), out-of-pocket patient costs, and societal cost of time off work (symptom diary).
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Aged 18 years or over
2. Consulting for an acute (<= 28 days) cough as the main presenting symptom
3. In the past 24 hours, the patient has had at least one of the screening symptoms listed below (a-d), localizing to the lower respiratory tract and suggestive of an acute lower respiratory tract infection (RTI):
3.1. Phlegm (sputum)
3.2. Chest pain
3.3. Shortness of breath
4. Patient and practice have sufficient time for consent and randomisation into the trial by the end of today
5. Patient able and willing to give informed consent themselves
6. Patient able and willing to complete the daily symptom diary themselves
7. Patient able and willing to receive weekly telephone calls from the trial team
Target number of participants
UK Sample Size: 436
Participant exclusion criteria
1. Known lung cancer or chronic lung disease (e.g. cystic fibrosis, COPD, bronchiectasis)
2. Has an 'active' diagnosis of asthma (for which any treatment has been given in the past 5 years)
3. The patient's RTI warrants same day hospital admission or immediate antibiotics (NB: use of delayed prescription does not preclude OSAC trial participation):
According to NICE guidelines, the patient warrants immediate antibiotic treatment by virtue of ONE OR MORE of the following:
1. Is clinically very unwell or has symptoms and signs suggestive of pneumonia, e.g. tachypnoea (>20bpm), unilateral chest signs or consolidation, or hypoxia (oxygen saturation <94%) or other systemic infection, e.g. suspected bacteraemia OR
2. Is at high risk of complications, including patients with chronic heart, chronic lung (e.g. COPD, bronchiectasis and cystic fibrosis), chronic renal, chronic liver or neuromuscular disease or immunosuppression; or with complications from previous episodes of lower respiratory tract infection, e.g. hospital admission for pneumonia OR
Aged over 65 years with at least TWO of the following criteria, or aged over 80 years with at least ONE of the following criteria:
1. Unplanned hospitalisation within the previous year
2. Type 1 or Type 2 diabetes
3. History of cardiac failure
4. Requires an antibiotic today to treat another infection unrelated to their acute cough, e.g. a co-existing cellulitis
5. Recently (<=1 month) used inhaled corticosteroids
6. Recently (<=1 month) used short (up to 2 weeks) course systemic corticosteroids
7. Currently using, or has previously (<=12 months) used systemic steroids for a cumulative period greater than 2 weeks, i.e. 'long-term' use
8. Known to be pregnant, is trying to conceive or is at risk of pregnancy (e.g. unwilling to take a reliable form of contraception) in the next month
9. Currently breast-feeding
10. This is not the patient's usual practice, i.e. patient is visiting or is not intending to stay with the practice for the 3 month trial follow up period
11. Previously randomised in the OSAC trial
12. Has been involved in another medicinal trial within the last 90 days or any other clinical research study within the last 30 days
13. Is unable to give informed consent or complete the trial paperwork (including the symptom diary) through mental incapacity, e.g. major current psychiatric illness, learning difficulties and dementia
14. Known immune-deficiency, e.g. chemotherapy causing immunosuppression, asplenia or splenic dysfunction, advanced cancer or HIV infection
15. Has any of the following known contra-indications or cautions to oral steroids current OR previous history of:
15.1. Peptic ulcer disease
15.3. Previous TB
15.5. No previous chickenpox AND known recent (<=28 days) history of close personal contact with chickenpox OR herpes zoster
15.6. Suspected ocular herpes simplex
15.7. Cushing's disease
15.9. Known allergy to prednisolone or other OSAC trial tablet ingredients (potato starch, lactose monohydrate, colloidal silicon dioxide, sodium starch glycolate, magnesium stearate), galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
15.10. Severe affective disorders, e.g. manic depression, previous steroid psychosis
15.11. Previous steroid myopathy
15.12. Intention to use a live vaccine in the next 3 months (NB: assess live vaccine status by cross-checking with BNF)
Current history only:
15.13. Uncontrolled diabetes (HbA1C > 8%)
15.14. Taking other interacting medication (e.g. phenytoin and anti-coagulants)
15.15. Uncontrolled hypertension
15.16. Any other BNF listed contra-indication or caution
15.17. Is unable to swallow tablets
Clinicians will be asked to use the British National Formulary (BNF) and their clinical prescribing systems to check for significant interactions for all patients. A SOP will be produced to describe the checking process.
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Department of Social Medicine
University of Bristol (UK)
National Institute for Health Research (NIHR) (UK) - School for Primary Care Research
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25778570