Oral Amoxicillin versus Benzyl Penicillin for Severe Pneumonia among Kenyan Children: A Pragmatic Randomized Controlled Non-inferiority Trial.


Agweyu, A; Gathara, D; Oliwa, J; Muinga, N; Edwards, T; Allen, E; Maleche-Obimbo, E; English, M; Severe Pneumonia Study Group, ; , COLLABORATORS; Aweyo, F; Awuonda, B; Chabi, M; Isika, N; Kariuki, M; Kuria, M; Mandi, P; Masibo, L; Massawa, T; Mogoa, W; Mutai, B; Muriithi, G; Ng'arng'ar, S; Nyamai, R; Okello, D; Oywer, W; Wanjala, L; (2015) Oral Amoxicillin versus Benzyl Penicillin for Severe Pneumonia among Kenyan Children: A Pragmatic Randomized Controlled Non-inferiority Trial. Clinical infectious diseases, 60 (8). pp. 1216-24. ISSN 1058-4838 DOI: https://doi.org/10.1093/cid/ciu1166

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Abstract

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.<br/> 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%.<br/> 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.<br/> 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.<br/> CLINICAL TRIAL REGISTRATION: NCT01399723.<br/>

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Epidemiology and Population Health > Dept of Medical Statistics
Research Centre: Tropical Epidemiology Group
PubMed ID: 25550349
Web of Science ID: 353715600013
URI: http://researchonline.lshtm.ac.uk/id/eprint/2155836

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