Community-acquired pneumonia Respiratory
Conditions
Interventions
Current interventions as of 21/02/2017:
Children will be enrolled from Paediatric Emergency Departments (PEDs) at university centres (main sites) and from the wards of the main sites a
Sponsors
University College London (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 31/05/2019: PED: 1. Age greater than 6 months and weighing 6 - 24kg 2. Clinical diagnosis of CAP at presentation to PED as defined by all of the following: 2.1 Presence of cough (reported by parents/guardians within 96 hours prior to presentation) AND 2.2 Temperature =38oC measured by any method OR likely fever within 48 hours prior to presentation AND 2.3 Signs of laboured/difficult breathing or focal chest signs at presentation in the PED (i.e. one or more of the following): 2.3.1 Nasal flaring 2.3.2 Chest retractions 2.3.3 Abdominal breathing 2.3.4 Focal dullness to percussion 2.3.5 Focal reduced breath sounds 2.3.6 Crackles with asymmetry 2.3.7 Lobar pneumonia on chest X-ray (if obtained) 3. Prior antibiotic treatment: 3.1 Not on systemic antibiotic treatment at presentation OR 3.2 Treated in the community as an outpatient with uninterrupted oral beta-lactam antibiotics for =48 hours 4. Decision to treat with oral amoxicillin for CAP on discharge from hospital 5. Parent/guardian willing to accept all possible randomised allocations 6. Available for follow up for the entire study period, parent/guardian willing to be contacted by telephone at day 4, weeks 1, 2 and 3, and attend a face-to-face follow up visit at 4 weeks after randomisation, unless discussed with MRC CTU 7. Informed consent form for trial participation signed by parent/guardian. WARD: 1. Age greater than 6 months and weighing 6 - 24kg. 2. Clinical diagnosis of CAP at presentation to hospital as defined by all of the following: 2.1 Presence of cough (reported by parents/guardians within 96 hours prior to presentation) AND; 2.2 Temperature =38oC measured by any method OR likely fever within 48 hours prior to presentation AND; 2.3 Signs of laboured/difficult breathing or focal chest signs (i.e. one or more of the following): 2.3.1 Nasal flaring 2.3.2 Chest retractions 2.3.3 Abdominal breathing 2.3.4 Focal dullness to percussion 2.3.5 Focal reduced breath sounds 2.3.6 Crackles with asymmetry 2.3.7 Lobar pneumonia on chest X-ray (if obtained) 3. Prior antibiotic treatment including doses administered in hospital (see Figure 2): 3.1 Treated in-hospital only with any oral or intravenous beta-lactam for =48 hours after admission 3.2 Treated initially in the community and subsequently in hospital with any oral or intravenous beta-lactam, without interruption, for =48 hours in total 4. Decision to further treat with oral amoxicillin for CAP on discharge from hospital 5. Child is considered fit for discharge at time of randomisation 6. Available for follow up for the entire study period, parent/guardian willing to be contacted by telephone at weeks 1, 2 and 3 and attend face-to-face follow up visit at 4 weeks after randomisation, unless discussed with MRC CTU 7. Parent/guardian willing to a
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 31/05/2019: PED: 1. Severe underlying chronic disease with an increased risk of developing complicated CAP 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 amoxicillin 4. Need for systemic treatment with an antibiotic other than amoxicillin on discharge from hospital 5. Bilateral wheezing without focal chest signs (most likely to represent respiratory tract infection of non-bacterial aetiology) 6. Complicated pneumonia 7. Receipt of initial antibiotic treatment in hospital in PAU or on the ward* 8. Parents/guardians unlikely to reliably complete the diary because of significant language barriers. WARD: 1. Severe underlying chronic disease with an increased risk of complicated CAP 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. Bilateral wheezing without focal chest signs (most likely to represent respiratory tract infection of non-bacterial aetiology) 5. Complicated pneumonia 6. Receipt of antibiotic other than a beta-lactam during admission 7. If treated in the community prior to admission, receipt of a non-beta-lactam antibiotic in the community at presentation 8. Clinically relevant positive blood culture (i.e. positive blood culture and clinical decision to prolong intravenous treatment for more than 48 hours or inappropriate to switch to amoxicillin therapy) 9. Receipt of >48 hours oral or intravenous antibiotic treatment in total 10. Decision to treat with oral antibiotic other than amoxicillin on discharge from hospital 11. Parents/guardians unlikely to reliably complete the diary because of significant language barriers. Previous participant exclusion criteria from 05/07/2018 to 31/05/2019: 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. Need for system treatment with an antibiotic other than amoxicillin on discharge from hospital 5. Bilateral wheezing without focal chest signs (most likely to represent respiratory tract infection of non-bacterial aetiology) 6. Complicated pneumonia 7. Receipt of initial antibiotic treatment as inpatient in PAU or on the ward 8. Parent/ guardians unlikely to reliably complete the diary because of significant language barriers 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 05/07/2018: The primary outcome is defined as any systemic antibacterial treatment in addition to the allocated trial medication as an inpatient or outpatient up to and including week 4 final follow-up. This includes re-treatment, increase in amoxicillin dose, extension of treatment and treatment with additional agents. Previous primary outcome measure: 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
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 05/07/2018: 1. Morbidity assessed using: 1.1. Specified clinical adverse events, including thrush, skin rashes and diarrhoea assessed at weeks 1, 2, 3 and 4 (final visit) 1.2. Severity and duration of parent/guardian-reported CAP symptoms assessed using a validated symptom diary at days 1-7 and weeks 2, 3 and 4 1.3. Number of days off work for parents/guardians and number of days away from out-of-home child care (where relevant), assessed using the parent diary on day 7 and day 14 2. Phenotypic resistance to penicillin at week 4 measured through microbiological analysis of S. pneumoniae isolates colonising the nasopharynx from nasopharyngeal samples at the baseline, final visit and any unscheduled visits 3. Adherence to trial drug assessed on days 1-7 via the parent diary and at follow up visit at week 1 or 4 4. Antibiotic use, collected at weeks 1, 2, 3 and 4, assessed using: 4.1. Cumulative number of additional courses of antibiotics 4.2. Total number of days of re-treatment with antibiotics 5. Health-economic outcomes assessed at day 7 and day 14 through the parent diary and at days 7, 15, 22 and 29 on follow up calls/visits: 5.1. Quality of life (using EQ-5D adapted for use in the paediatric population) assessed at weeks 1, 2, 3 and 4 (final visit) 5.2. Cost-causing events and associated resource use, including costs based on patient admission and discharge dates, treatment costs and costs associated with treatment failure such as re-admissions and re-treatments. Assessed through completion of a table of the number of times contacted and number of times visited for A&E/walk-in centres, out of hours service, paediatrician, GP practice, pharmacist, NHS direct/NHS 111 Previous secondary outcome measures: | — |
Countries
England, United Kingdom
Contacts
Public ContactSam Barratt
Outcome results
None listed