PIVOT: IV vs Oral antibiotics for Pneumonia Journal Club April 2012 Chris Edwards Introduction • What is your clinical practise with moderate to severe pneumonia? • “48 hours IVs and then home on orals if culture negative.” • But this doesn’t make sense …. Plan • • • • • • PICO Search Result Trial Analysis Summary Discussion PICO • • • • P- children with pneumonia I – Oral antibiotics C – IV antibiotics O- time to recovery/time in hospital Search • • • • • • • Medline “pneumonia AND antibiotics” RCTs Children (0-18 years) English language ~80 hits Then looked for developed world(few) rather than developing world (lots) Result • Comparison of oral amoxicillin and intravenous benzylpenicillin for community acquired pneumonia in children(PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial • M Atkinson, M Lakhanpaul, A Smyth, H Vyas, V Weston, J Sithole, V Owen, K Halliday, H Sammons, J Crane, N Guntupalli, L Walton, T Ninan, A Morjaria, T Stephenson • Thorax 2007;62:1102–1106. doi: 10.1136/thx.2006.074906 Analysis Analysis “A study was undertaken to ascertain whether therapeutic equivalence exists for treatment of community acquired pneumonia by the oral and IV route.” Population: Children, but no upper age limit was specified. Intervention: IV v Oral antibiotics Outcomes: “therapeutic equivalence” taken as: Primary outcome measure was time from randomisation until the temperature was <38°C for 24 continuous hours and oxygen requirement had ceased Secondary outcomes: included time in hospital, complications (empyema, readmission, further courses of antibiotics), duration of oxygen requirement time to resolution of illness. Analysis Yes “A block randomisation sequence stratified by centre was produced using a random number generator. The sequence was accessed via the internet, therefore allowing concealment of allocation. Children were randomly assigned to oral amoxicillin (chosen in preference to oral penicillin owing to the superior absorption and palatability) or IV benzyl penicillin.” So not double blind. Analysis • Yes…. Analysis Analysis • No. • Could have cannulated all, given placebo IV to the oral group and oral placebo to the IV group… Analysis • Yes Analysis Analysis Children in the IV group were changed to oral amoxicillin on discharge or sooner if the clinical team considered their improvement warranted this. Both groups completed a 1-week course of antibiotics in total. IV group more likely to require another antibiotic / rescue medication. ?Does this mean there was an inherent difference in the two groups? Analysis Analysis • • • • • Time to temperature less than 38.5 Length of time in oxygen Time to discharge Time to resolution of symptoms Number of complications Analysis Analysis Analysis Time in hospital and oxygen requirement “The median length of hospital stay was significantly shorter in the oral group than in the IV group (1.77 days (25th–75th centile 1.2– 2.0) and 2.1 days (25th–75th centile 1.8–2.9),respectively, p,0.001). We also calculated the median of the differences and this was found to be 0.60 days (0.15–1.13) (IV– oral). “ Oxygen During admission, 18/103 children (17.5%) in the IV group and 28/100 children (28%) in the oral group required oxygen (p=0.07). The duration of oxygen requirement was significantly longer in the IV group than in the oral group (median 20.5 vs 11.0 hours, p=0.04). Children randomised to IV treatment received a median of 6 doses (25th–75th centile 4.7–7.5) of IV benzyl penicillin before conversion to oral amoxicillin. Analysis • For the primary outcome measure, all p values are for equivalence. Therefore, a p value of ,0.05 indicates that the null hypothesis (a difference of .20% exists between the two treatments) has been disproved. Analysis • Yes – Nottingham isn’t that far away (especially now they widened the M1). Analysis • ? Chest X-ray resolution? • ?Longer follow up? • ?Lung function? Probably wouldn’t make a difference to the decision re: treatment. Analysis • The change in practise maybe to start oral amoxicillin in AAU and keep overnight. If remains well, then home, vs • IV for 48 hours then home. So the benefit probably does outweigh the costs. Summary • Oral antibiotics appear to be equivalent to IV antibiotics for pneumonia • Pts on IV antibiotics appear to have more complications Discussion • Would you encourage the team to change practice in AAU?