Paediatric community-acquired pneumonia Respiratory Pneumonia, unspecified
Conditions
Interventions
Open-label parallel-group 2 x 5 factorial randomised trial assessing 2 different oral step-down antibiotics (amoxicillin and co-amoxiclav (amoxicillin:clavulanate 7:1)) given after intravenous antibio
Sponsors
PENTA Foundation
Eligibility
Sex/Gender
All
Age
2 Months to 6 Years
Inclusion criteria
Inclusion criteria: 1. Aged 2 months to 6 years inclusive 2. Weighing >= 3 kg and <30 kg 3. Admitted to hospital with severe pneumonia judged to require at least 24h of intravenous antibiotics by the treating physician 4. Difficulty breathing (with or without cough reported by parent/carer) PLUS one or more of 4.1. Central cyanosis or hypoxaemia (room air pulse oximetry <90%) 4.2. Any sign of severe respiratory distress (e.g. severe chest indrawing, grunting, nasal flaring, head nodding) 4.3. Signs of pneumonia (fast breathing (defined as respiratory rate =50 breaths per minute at age 2-11 months and =40 breaths per minute at age 1 years or older) or chest indrawing) PLUS a general danger sign (inability to breastfeed or drink, lethargy or reduced level of consciousness, convulsions) occurring at any time from admission up to randomisation. 5. About to initiate or already initiated intravenous benzylpenicillin plus gentamicin, ampicillin plus gentamicin, benzylpenicillin or ampicillin alone, ceftriaxone alone or cefotaxime alone 6. Received at most 24h of these intravenous antibiotics at the point of randomisation (that is, first dose of any intravenous antibiotics must have been administered no more than 24h previously at randomisation) 7. Parent/carer willing to accept and adhere to all possible randomised allocations for their child, including 5 days of intravenous antibiotics, and signed written informed consent available from parent/carer 8. Available for follow-up for the entire study period; specifically, parent/carer willing to return with their child to clinic at 4 weeks, and be contacted at minimum by telephone at weeks 1, 2 and 3 For children enrolled in PK (Section 10.1) or microbiology (Section 10.2) substudies, additional inclusion criteria are: 9. If undergoing additional PK sampling: willing to provide samples and potentially to stay in hospital for up to an additional 12h (separate consent will be obtained for PK sampling which may be refused and the child still join the main trial (PediCAP-A): consent for PK sampling is required for inclusion in the Phase II PK trial (PediCAP-B))
Exclusion criteria
Exclusion criteria: 1. Point-of-care semi-quantitative C-reactive protein (CRP) test 48h post-admission) 3. Admitted to hospital overnight in the last 28 days (possibility of nosocomially-acquired pneumonia) 4. Known or anticipated need for invasive ventilation or admission to intensive care 5. Clinician considers this episode to be predominantly due to reactive airways disease (e.g. asthma) (wheeze responsive to bronchodilators, see Manual of Operations (MOP) for more details) 6. Clinician considers this episode to be due to viral bronchiolitis alone in a child under 1 year 7. Documented penicillin allergy or contra-indications to penicillin/amoxicillin/co-amoxiclav 8. Anticipated need for systemic treatment with an antibiotic other than trial regimens during hospital admission or in the following 28 days (e.g. for Pneumocystis jiroveci) 9. On long-term antibiotics for prophylaxis or treatment (e.g. for tuberculosis treatment or cotrimoxazole prophylaxis for HIV infection) 10. Previously enrolled in PediCAP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For the main trial (PediCAP-A): Hospital readmission occurring from the date of initial discharge to day 28 or death (all-cause) occurring from the date of randomisation to day 28 For the Phase II PK trial (PediCAP-B): Plasma exposure to amoxicillin and clavulanate measured using LC-MS/MS methods in samples taken when children start oral antibiotics | — |
Secondary
| Measure | Time frame |
|---|---|
| For the main trial (PediCAP-A), within 28 days of randomisation: 1. CAP-related readmission occurring at any time from the date of initial discharge to day 28 or CAP-related mortality occurring at any time from the date of randomisation to day 28 2. Length of stay required during the index hospitalisation calculated from the date of randomisation to the initial date of discharge, and overall through 28 days calculated from the date of randomisation to the initial date of discharge plus any additional days of hospitalisation from the date of discharge to day 28 3. Mortality (all-cause) occurring at any time during the 28 days of trial follow-up 4. Duration of supplemental oxygen during the index hospitalisation calculated from the date of randomisation to the date of discharge 5. Total days of antibiotic exposure through 28 days calculated from the date of randomisation to day 28 6. Modification of randomised antibiotics for any reason except early stopping or receipt of subsequent course of antibiotics for any reason occurring at any time during the 28 days of trial follow-up 7. Modification of randomised antibiotics for inadequate response or additional courses for CAP relapse occurring at any time during the 28 days of trial follow-up 8. Serious adverse events occurring at any time during the 28 days of trial follow-up 9. Grade 3 or 4 adverse events occurring at any time during the 28 days of trial follow-up 10. Adverse events of any grade related to antibiotics occurring at any time during the 28 days of trial follow-up 11. Key solicited events, specifically diarrhoea, vomiting and gastrointestinal disorders, skin rash, thrush/candida occurring at any time during the 28 days of trial follow-up 12. Modification of antibiotics for adverse reactions occurring at any time during the 28 days of trial follow-up 13. Specific clinical complications, including sepsis, lung abscess, empyema occurring at any time during the 28 days of trial follow-up 14. Line complications | — |
Countries
Mozambique, South Africa, Uganda, Zambia, Zimbabwe
Outcome results
None listed