The effectiveness, safety and duration of step-down oral antibiotics for children hospitalised with severe pneumonia

Phase 2

• Conditions: Paediatric community-acquired pneumonia; Respiratory; Pneumonia, unspecified

• Registration Number: ISRCTN63115131
• Lead Sponsor: PENTA Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-05-15
• Last Update Posted: 29 July 2024
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 1231

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

1. Point-of-care semi-quantitative C-reactive protein (CRP) test < 10 mg/l at screening (very unlikely to represent severe pneumonia requiring antibiotics)
2. Likely nosocomial pneumonia (onset >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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
For the main trial (PediCAP-A):<br>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<br><br>For the Phase II PK trial (PediCAP-B):<br>Plasma exposure to amoxicillin and clavulanate measured using LC-MS/MS methods in samples taken when children start oral antibiotics