Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial


Clin Infect Dis

BACKGROUND: There are concerns that the evidence from studies showing noninferiority of oral amoxicillin to benzyl penicillin for severe pneumonia may not be generalizable to high-mortality settings. METHODS: An open-label, multicenter, randomized controlled noninferiority trial was conducted at 6 Kenyan hospitals. Eligible children aged 2-59 months were randomized to receive amoxicillin or benzyl penicillin and followed up for the primary outcome of treatment failure at 48 hours. A noninferiority margin of risk difference between amoxicillin and benzyl penicillin groups was prespecified at 7%. RESULTS: We recruited 527 children, including 302 (57.3%) with comorbidity. Treatment failure was observed in 20 of 260 (7.7%) and 21 of 261 (8.0%) of patients in the amoxicillin and benzyl penicillin arms, respectively (risk difference, -0.3% [95% confidence interval, -5.0% to 4.3%]) in per-protocol analyses. These findings were supported by the results of intention-to-treat analyses. Treatment failure by day 5 postenrollment was 11.4% and 11.0% and rising to 13.5% and 16.8% by day 14 in the amoxicillin vs benzyl penicillin groups, respectively. The most frequent cause of cumulative treatment failure at day 14 was clinical deterioration within 48 hours of enrollment (33/59 [55.9%]). Four patients died (overall mortality 0.8%) during the study, 3 of whom were allocated to the benzyl penicillin group. The presence of wheeze was independently associated with less frequent treatment failure. CONCLUSIONS: Our findings confirm noninferiority of amoxicillin to benzyl penicillin, provide estimates of risk of treatment failure in Kenya, and offer important additional evidence for policy making in sub-Saharan Africa. CLINICAL TRIAL REGISTRATION: NCT01399723.

Agweyu, A., Gathara, D., Oliwa, J., Muinga, N., Edwards, T., Allen, E., Maleche-Obimbo, E., English, M., Severe Pneumonia Study, Group

Pages:1216-24, Volume:60, Edition:1/1/2015, Date,Apr-15

Link: https://www.ncbi.nlm.nih.gov/pubmed/25550349

Notes:Agweyu, Ambrose|Gathara, David|Oliwa, Jacquie|Muinga, Naomi|Edwards, Tansy|Allen, Elizabeth|Maleche-Obimbo, Elizabeth|English, Mike|eng|076827/Wellcome Trust/United Kingdom|084538/Wellcome Trust/United Kingdom|MR/K012126/1/Medical Research Council/United Kingdom|097170/Wellcome Trust/United Kingdom|Wellcome Trust/United Kingdom|092654/Wellcome Trust/United Kingdom|Comparative Study|Multicenter Study|Randomized Controlled Trial|Research Support, Non-U.S. Gov’t|2015/01/01 06:00|Clin Infect Dis. 2015 Apr 15;60(8):1216-24. doi: 10.1093/cid/ciu1166. Epub 2014 Dec 30.

ISBN: 1537-6591 (Electronic)|1058-4838 (Linking) Permanent ID: PMC4370168 Accession Number: 25550349

Author Address: Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi.|Medical Research Council Tropical Epidemiology Group, Department of Infectious Disease Epidemiology.|Department of Medical Statistics, London School of Hygiene and Tropical Medicine, United Kingdom.|Department of Paediatrics and Child Health, University of Nairobi, Kenya.|Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi Nuffield Department of Medicine, University of Oxford, United Kingdom.