Condition category
Respiratory
Date applied
14/12/2015
Date assigned
15/12/2015
Last edited
15/12/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Pneumonia (an infection of the lungs) is one of most common infections in young children worldwide. Because there are no good tests to clearly identify whether pneumonia is caused by bacteria in children, the decision to prescribe antibiotics has to be made based on clinical assessment. Therefore 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. 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.

Who can participate?
Parents or carers of children aged 1-5 are 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.

What does the study involve?
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 treatment and up to twice during and after treatmen, 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.

What are the possible benefits and risks of participating?
The potential benefits of participating are:
1. Dosing of medication is more accurate because it is based on the child’s weight.
2. Participants are contacted by the study nurse weekly during the study i.e. participants have more follow-up than normal for a child with pneumonia. Participants are also given a phone number for the study team in case of questions or concerns.
3. The improved understanding of the impact of amoxicillin duration and dose on the development of antibiotic resistance, together with evidence of the effectiveness of different courses, will enable the most appropriate treatment to be identified.
The potential drawbacks of participating are:
1. Amoxicillin given for 3 days may not be as good at treating pneumonia as treatment for 7 days. We think this is unlikely and shorter treatment has been shown to be safe in adults.
2. Participants need to come to the hospital for two extra visits with the study nurse at the end of weeks 1 and 4.

Where is the study run from?
St George's Hospital (UK).

When is the study starting and how long is it expected to run for?
May 2015 to May 2018.

Who is funding the study?
National Institute for Health Research (HTA).

Who is the main contact?
Jennifer Petrie
mrcctu.capit@ucl.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Jennifer Petrie

ORCID ID

Contact details

MRC CTU at UCL
Aviation House
125 Kingsway
London
WC2B 6NH
United Kingdom
+44 (0)207 670 4796
mrcctu.capit@ucl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 13/88/11

Study information

Scientific title

Efficacy, safety and impact on antimicrobial resistance of duration and dose of amoxicillin treatment for young children with community-acquired pneumonia (CAP): a randomised controlled trial

Acronym

CAP-IT

Study hypothesis

1. Lower dose (35-50 mg/kg per day given in two divided doses) oral amoxicillin treatment is non-inferior to higher dose (70-120 mg/kg per day in two divided doses) amoxicillin treatment for uncomplicated childhood community-acquired pneumonia (CAP) in terms of resolution/prevention of relapse of lower respiratory illness requiring retreatment with antibiotics.
2. Shorter duration (3 days) amoxicillin treatment is non-inferior to longer duration (7 days) amoxicillin treatment for uncomplicated childhood CAP.

More details can be found here: http://www.nets.nihr.ac.uk/projects/hta/138811

Ethics approval

Submission pending Jan/Feb 2016

Study design

Multi-centre UK-based randomised double-blind placebo-controlled 2x2 factorial non-inferiority trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Community-acquired pneumonia

Intervention

Children will be enrolled from Paediatric Emergency Departments (PEDs) at university centres (main sites) and from the wards of the main sites and their affiliated secondary care hospitals (satellite sites).

Participants will be randomised to:
Randomisation 1: Lower dose (35-50 mg/kg per day given in two divided doses) oral amoxicillin treatment versus higher dose (70-120 mg/kg per day in two divided doses) oral amoxicillin treatment. Dose volumes will be identical in the lower and higher dose groups.
Randomisation 2: Three days of oral amoxicillin followed either by placebo for 4 days (3 days active treatment) or by a further 4 days of amoxicillin (7 days active treatment).

This will result in four treatment groups:
1. Longer/lower dose: 7 days at 35-50 mg/kg/day
2. Shorter/lower dose: 3 days at 35-50 mg/kg/day
3. Longer/higher dose: 7 days at 70-120 mg/kg/day
4. Shorter/higher dose: 3 days at 70-120 mg/kg/day

Intervention type

Drug

Phase

Phase III

Drug names

Amoxicillin

Primary outcome measures

Any antibiotic treatment prescribed in addition to the allocated trial medication as an in- or out-patient up to and at final follow-up. This includes retreatment, extension of treatment and treatment with additional agents. Measured at weeks 1, 2, 3 and 4.

Secondary outcome measures

1. Adverse events assessed at weeks 1, 2, 3 and 4 (final visit)
2. Severity and duration of parent-reported CAP symptoms assessed using a validated symptom diary at days 1-7 and weeks 2, 3 and 4
3. Health economics measured using EQ-5D adapted for use in the paediatric population at weeks 1, 2, 3 and 4 (final visit)
4. Details of additional courses of antibiotics and total number of days of re-treatment with antibiotics to be collected at weeks 1, 2, 3 and 4
5. Adherence to be assessed on days 1-7 via the parent diary and at follow up visit at week 1 or 4
6. Samples to assess for penicillin resistance will be collected at baseline, week 1 (during the pilot phase) and week 4

Overall trial start date

01/05/2015

Overall trial end date

30/05/2018

Reason abandoned

Eligibility

Participant inclusion criteria

The inclusion criteria differ between the PED and WARD group patients and these are presented separately for clarity.

PED group:
1. Age from 1 to 5 years (up to their 6th birthday)
2. Clinical diagnosis of CAP as defined by the following (note: all four criteria must be met for the child to be eligible):
2.1. Presence of cough (reported by parents/guardians in last 96 hours)
2.2. Temperature ≥38oC measured by any method or history of fever in last 24 hours reported by parents/guardians
2.3. Increased age-specific respiratory rate (first or second triage or clinical examination by a member of clinical staff)
2.4. Signs of laboured/difficult breathing or focal chest signs at presentation in the PED (one or more of the following):
2.4.1. Nasal flaring
2.4.2. Chest retractions
2.4.3. Abdominal breathing
2.4.4. Focal dullness to percussion
2.4.5. Focal reduced breath sounds
2.4.6. Focal crackles
3. Decision to treat with oral amoxicillin for CAP
4. Decision to be discharged from the paediatric emergency department immediately
5. Parent/guardian willing to accept all possible randomised allocations
6. Available for follow up for the entire study period and parent/guardian willing to be contacted by telephone
7. Informed consent form for trial participation signed by parent/guardian.

WARD group:
1. Age from 1 to 5 years (up to their 6th birthday)
2.1. Presence of cough (reported by parents/guardians in last 96 hours)
2.2. Temperature ≥38oC measured by any method or history of fever in last 24 hours reported by parents/guardians
2.3. Increased age-specific respiratory rate (first or second triage or clinical examination by a member of clinical staff)
2.4. Signs of laboured/difficult breathing or focal chest signs (one or more of the following):
2.4.1. Nasal flaring
2.4.2. Chest retractions
2.4.3. Abdominal breathing
2.4.4. Focal dullness to percussion
2.4.5. Focal reduced breath sounds
2.4.6. Focal crackles
3. Child admitted to a paediatric assessment unit or inpatient ward at a participating hospital (main site or satellite site).
4. Decision to treat with antibiotics during the ≤48 hours after admission with oral or intravenous amoxicillin or co-amoxicillin
5. Child planned for discharge on the same day as randomisation
6. Available for follow up for the entire study period and parent/guardian willing to be contacted by telephone
7. Parent/guardian willing to accept all possible randomised allocations
8. Informed consent for trial participation signed by a parent/guardian

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

2400

Participant exclusion criteria

The exclusion criteria differ between the PED and WARD group patients and these are presented separately for clarity.

PED group:
1. Severe underlying chronic disease including sickle cell anaemia, primary or secondary immunodeficiency, chronic lung disease and cystic fibrosis
2. Documented penicillin allergy
3. Any other known contra-indication to taking amoxicillin
4. Already on antibiotic treatment at presentation
5. Wheezing (most likely to represent respiratory tract infection of non-bacterial aetiology)
6. Complicated pneumonia
7. Antibiotic exposure within the last month
8. Weight is >24kg

WARD group:
1. Severe underlying chronic disease including sickle cell anaemia, primary or secondary immunodeficiency, chronic lung disease and cystic fibrosis
2. Documented penicillin allergy
3. Any other known contra-indication to taking amoxicillin
4. Already on antibiotic treatment at presentation
5. Wheezing (most likely to represent respiratory tract infection of non-bacterial aetiology)
6. Complicated pneumonia
7. Antibiotic exposure within the last month
8. Clinically relevant positive blood culture (i.e., positive blood culture and clinical decision to prolong intravenous treatment for more than 48 hours or to switch to antibiotic therapy other than co-amoxicillin/amoxicillin)
9. Persistent or increasing oxygen requirement at ≤48 hours of admission compared with on admission
10. Persistent or deteriorating tachypnoea at ≤48 hours of admission compared with on admission
11. Receipt of non-amoxicillin-based therapy since admission (either as combination therapy with amoxicillin or as standalone antibiotic therapy)
12. Receipt of >48 hours oral or intravenous inpatient antibiotic treatment
13. Decision to treat with oral antibiotic other than amoxicillin on discharge from hospital
14. Weight is >24kg

Recruitment start date

01/09/2016

Recruitment end date

30/04/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St George's Hospital
SW17 0QT
United Kingdom

Sponsor information

Organisation

University College London (UK)

Sponsor details

Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To achieve the greatest possible dissemination the results will be communicated using appropriate channels to: 1. Antibiotic prescribers: Open Access publication in high impact peer-review journals likely to be read by healthcare professionals involved in the management of CAP in children in the UK
2. Policymakers/stakeholders: An annual newsletter will be published and relevant findings summarised for key stakeholders such as the Royal Colleges, relevant Commissioners of children’s services and participating networks
3. British National Formulary for Children: Members of the CAP-IT study team are lead clinical advisors for the BNFC on anti-infectives
4. Funders: A final report will be prepared for the HTA
5. Public/parents: A project website will be developed and information made available there. In addition, press releases will be generated at key points to make relevant information about CAP-IT available to the general public. Finally, the families of all participants will be informed of the trial results by email or post.

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes