Chlorproguanil-dapsone is more effective, but causes more adverse events compared with sulfadoxine pyrimethamine in children with uncomplicated falciparum malaria

Evidence-Based Healthcare & Public Health (2004) 8, 373–374 ARTICLE IN PRESS KEYWORDS Malaria; Children; Africa; Chlorproguanil- dapsone; Sulfadoxine- pyrimethamine; Treatment resistance; Randomised controlled trial www.elsevier.com/locate/ebhph $Abstracted from: Alloueche A, Bailey W, Barton S et al. Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial. Lancet 2004; 1744-2249/$ - see front matter & 2004 Published by Elsevier Ltd. doi:10.1016/j.ehbc.2004.09.009 363: 1843–1848. Study Parameters Question How does the safety and efficacy of chlorproguanil-dapsone compare with sulfadoxine pyrimethamine in treatment of uncomplicated falciparum malaria in young African children? Study design Randomised double blind controlled trial. Setting Five countries in Africa (Tanzania, Kenya, Malawi, Nigeria and Gabon); March to December 2000. Summary Question How does the safety and efficacy of chlorproguanil-dapsone compare with sulfadoxine-pyrimethamine in treating uncomplicated falciparum malaria in young African children? Study Design Randomised double blind controlled trial. Main Results Chlorproguanil-dapsone was significantly more effictive compared with sulfadoxine-pyrimethamine in African children with uncomplicated falciparum malaria at two weeks. However, treatment related adverse events were also significantly more common with chlorproguanil-dapsone compared with sulfadoxine- pyrimethamine (see Results table). Authors’ Conclusions Where resistance to sulfadoxine-pyrimethamine is a pro- blem, chlorproguanil-dapsone could be an effective alternative in African children with uncomplicated falciparum malaria. & 2004 Published by Elsevier Ltd. EVIDENCE-BASED PUBLIC HEALTH Chlorproguanil-dapsone is more effective, but causes more adverse events compared with sulfadoxine pyrimethamine in children with uncomplicated falciparum malaria$ Results table Treatment outcomes (intention to treat analysis) Chlorproguanil- dapsone (n=1480) Sulfadoxine pyrimethamine (n=370) Significance (95% CI) Overall treatment success Overall treatment failure 1313 (96%) 53 (4%) 306 (89%) 37 (11%) OR 3.07 (1.97 to 4.78); po0.001 ARTICLE IN PRESS EVIDENCE-BASED PUBLIC HEALTH374 Adverse events: Related to study medication 168 (11%) 26 (7%) Treatment difference: 4.3% (1.3 to 7.4); p=0.015 Participants 1850 children aged 1 to 10 years (mean age 4.6 years). Inclusion criteria: Asexual Plasmodium falciparum parasitaemia between 2,000/and 100,000/mL. Exclusion criteria: severe malaria (parasitaemia4100,000/ mL and haemoglobin o65g/L); convulsions; concomitant infection/disease; allergy to sulphonamides; antimalarial traeatment within the previous 7 days and use of any ‘investigational’ drug within the previous 30 days. Intervention Children were randomised to chlorproguanil-dapsone (2.0mg/kg of chlorproguanil and 2.5mg/kg dapsone orally at 24 hour intervals for 3 days) or sulfadoxine-pyrimethamine (1.25mg/kg sulfadoxine and 25mg/kg pyrimethamine in a single dose). Follow up was after 2 weeks. Main outcomes Safety profile of chlorproguanil-dapsone, and treatment failure (defined by the WHO in-vivo test). Notes Randomisation was performed at a ratio of 4:1, CD:SP, in blocks of ten, stratified by site. Analysis was by intention to treat. At a 5% level of significance using a two-sided test, the study had480% power to detect a 5% difference between CD and SP in the incidence of adverse events and 490% power to detect a 15% difference in treatment failure rates. Smaller differences in effect sizes cannot be excluded on the basis of this study. Sources of funding: This study was funded by GlaxoSmithKline (GSK) Pharmaceuticals, the UK Department for International Development (DFID) and the World Health Organisation (WHO). Abstract provided by Bazian Ltd, London Chlorproguanil-dapsone is more effective, but causes more adverse events compared with sulfadoxine pyrimethamine in children with uncomplicated falciparum malaria Study Parameters Results table