MRC Clinical Trials Unit at UCL
Background and study aims
Pneumonia is one of most common infections on the lungs in young children worldwide. There are no good tests to clearly identify whether pneumonia is caused by bacteria in children; therefore decision to prescribe antibiotics has to be made based on clinical assessment. As a result antibiotics are very commonly prescribed to children for possible pneumonia. We know that treatment with antibiotics can lead to changes in the bacteria carried by the person taking them, making the bacteria become more resistant to the effect of the antibiotics. These resistant bacteria can subsequently cause an infection in the treated children or spread to other persons in close contact. Infections caused by resistant bacteria are more difficult to treat. The amount of antibiotic (dose) and the number of days of treatment (duration) is likely to have an effect on the development of resistant bacteria in individual patients. Currently we do not know which antibiotic treatment duration and dose are best for treating childhood pneumonia. Also the relationship between dose, duration and the development of resistant bacteria in the nose and gut (two preferred places where bacteria live) is not understood.
What is this study looking at?
This study will look at whether lower doses and shorter duration of antibiotic treatment with amoxicillin, the antibiotic most commonly used for pneumonia in children, are as good at treating pneumonia as higher doses and longer duration of treatment. The aim of the study is to investigate whether 3 days of treatment is as good as 7 days of treatment, and whether a low dose is as good as a high dose for treating pneumonia, and whether these different doses and durations affect the appearance of resistant bacteria. The lower dose and shorter treatment could reduce side effects and cause less resistance. The results of the study could inform how children in the UK and also in other countries should best be treated for pneumonia.
- Dose of amoxicillin - We will compare treatment with low-dose or high-dose amoxicillin. Both doses are considered safe and are currently being used in hospitals in the UK and internationally.
- Length of treatment - We will compare treatment with 3 days or 7 days of amoxicillin. There are some studies to suggest that 3 days of treatment could be as good as 7 days.
- Effect of amoxicillin on bacteria - We will look at which treatment option reduces the chance of antibiotic resistance affecting children treated with amoxicillin for pneumonia.
Who can participate?
Children, greater than 6 months, weighing 6 - 24 kg, who present to A&E or Paediatric Assessment Unit (PAU) in the UK with a clinical diagnosis of Community-Acquired Pneumonia (CAP) in whom the decision has been made to treat with antibiotics. Parents or carers of such children may be asked to join the study if the child has pneumonia and will be treated at home, as long as there are no signs of very severe pneumonia or other complications. Children seen in the emergency department who can go home can join the study immediately. Children in hospital often need a short period of intravenous treatment or observation; their carers would be invited to join the study after up to 48 hours of inpatient therapy.
Study treatment/What does the study involve?
Children who take part in CAP-IT will be given the antibiotic amoxicillin. Participating children are randomly allocated to be treated with either high or low dose amoxicillin for either 3 or 7 days. In order to treat the groups of children in the same way, neither the doctors nor the families know whether their child is receiving high or low dose amoxicillin. Similarly, while children receiving 7 days have amoxicillin every day, those receiving 3 days have 3 days of amoxicillin followed by 4 days of placebo (medicine with no active ingredients). We compare how frequently children have to be treated again with antibiotics in the different groups.
To look at the development of resistant bacteria, nose swabs are collected before starting antibiotic treatment and 4 weeks after starting study treatment, to find out whether shorter treatments and/or those using a specific dose lead to less resistant bacteria in the nose at the end of treatment.
Taking the treatment
The CAP-IT trial medication, amoxicillin (low/high)/placebo, is administered orally twice a day for 7 days. A total of 14 doses will be given in the duration of the trial. This is to be given to the child at home by a parent or carer.
Who is funding the study?
The CAP-IT trial is funded by the National Institute for Health Research Health Technology Assessment Programme (project number 13/88/11, www.nihr.ac.uk)
Who is the main study contact?
Please email the CAP-IT Trial Manager at: email@example.com
MRC Clinical Trials Unit at UCL
Professor Mike Sharland
St George’s University of London