A multicentre randomised controlled equivalence trial comparing oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children PIVOT Trial

Abstract

Objective To ascertain whether therapeutic equivalence exists for treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes. Design Multicentre pragmatic randomised controlled non-blinded equivalence trial. Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. Setting Eight paediatric centres in England (district general and tertiary hospitals). Participants 246 children who required admission to hospital and met the following 3 criteria for diagnosis of pneumonia: fever, respiratory symptoms or signs and radiologically confirmed pneumonia. Exclusion criteria were wheeze, oxygen saturations < 85% in air, shock requiring > 20mls/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age < 6 months. Intervention Children were randomised to oral amoxicillin (126) or IV benzyl penicillin (120). The oral group received 7 days oral treatment. The IV group were changed to oral amoxicillin after a median of 6 doses IV and received 7 days of antibiotics in total. Main Outcome Measures The pre-defined primary outcome measure was time for the temperature to be less than 38oC for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness. Results Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p=0.0001 for equivalence). Three children in the oral group were changed to IV antibiotics. Seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups. Conclusion The findings demonstrate that oral amoxicillin is effective for the majority of children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society (BTS) guidelines on childhood pneumonia could not draw on evidence to address this issue. Most importantly, this will spare children and their families the trauma and pain of cannulation and children spend less time in hospital. Trial Registration N0192107553 - National Research Register Key Words Pneumonia, paediatric, treatment, antibiotics