Comparison of Sulfadoxine‐Pyrimethamine, Unsupervised Artemether‐Lumefantrine, and Unsupervised Artesunate‐Amodiaquine Fixed‐Dose Formulation for Uncomplicated Plasmodium falciparum Malaria in Benin: A Randomized Effectiveness Noninferiority Trial

Background. We compared sulfadoxine‐pyrimethamine (SP) with unsupervised artemether‐lumefantrine (AL) and unsupervised amodiaquine‐artesunate (ASAQ) fixed‐dose formulation for the treatment of uncomplicated malaria in children in Benin. Methods. This open‐label, noninferiority comparative trial included children aged 6–60 months. The follow‐up period was 6 weeks, and the primary objective was a comparison of polymerase chain reaction (PCR)–adjusted effectiveness rates at day 28. Results. The study included 240 children (48 received SP, and 96 each received AL and ASAQ). The intention‐to‐treat analysis showed effectiveness rates on day 28 of 20.8%, 78.1%, and 70.5% for SP, AL, and ASAQ, respectively. After adjustment for PCR results, these rates were 27.1%, 83.3%, and 87.4%, respectively. The per‐protocol analysis (217 patients) showed effectiveness rates on day 28 of 21.7%, 88.0%, and 76.1% for SP, AL, and ASAQ, respectively. After adjustment for PCR results, these rates were 28.3%, 94.0%, and 93.2%, respectively. SP was less effective than the other drugs in the PCR‐adjusted analysis, whereas AL and ASAQ were equally effective. The rate of new infection was higher among children treated with ASAQ than among those treated with AL. Conclusions. This was the first trial, to our knowledge, to compare unsupervised AL with unsupervised ASAQ fixed‐dose formulation; both treatments provided high PCR‐adjusted day 28 effectiveness rates. Efficacy rates for SP were surprisingly low. Clinical trials registration. NCT00460369.