Safety outcomes.

a<p>Both TEAEs considered treatment-related were severe abnormal liver function tests, which were considered AESIs.</p>b<p>Determined by Chi-squared test.</p><p>Safety outcomes.</p

Estimates of comparative efficacy of ASAQ and AL for treatment of the first episode of malaria: Per protocol (PP) population.

<p>Values are for all subjects completing the first episode of the study according to protocol (PP population).</p>a<p>ASAQ was considered non-inferior to AL if the lower limit of the one-sided 95% confidence interval was>−5%.</p>b<p>P-value was determined by Fisher's exact test.</p>c<p>P-value was determined by Wilcoxon's signed-rank test.</p>d<p>P-value was determined by Chi-squared test.</p><p>Estimates of comparative efficacy of ASAQ and AL for treatment of the first episode of malaria: Per protocol (PP) population.</p

Parasite density.

<p>(A) Shows the mean parasite density in the ASAQ and AL groups between days 0 and 42 of the first episode. (B) Shows the mean parasite density in the ASAQ and AL groups at D0 for all episodes.</p

PCR-corrected ACPR rates.

<p>Shown is the percent of children in the ASAQ and AL groups with PCR-corrected ACPR on day 28 by month, ITT Population.</p

Baseline characteristics of patients.

<p>Values are for patients from ITT pop.</p><p>Baseline characteristics of patients.</p

Efficacy and Safety of Fixed-Dose Artesunate-Amodiaquine vs. Artemether-Lumefantrine for Repeated Treatment of Uncomplicated Malaria in Ugandan Children

<div><p></p><p>The safety and efficacy of the two most widely used fixed-dose artemisinin-based combination therapies (ACT), artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are well established for single episodes of uncomplicated <i>Plasmodium falciparum</i> malaria, but the effects of repeated, long-term use are not well documented. We conducted a 2-year randomized, open-label, longitudinal, phase IV clinical trial comparing the efficacy and safety of fixed-dose ASAQ and AL for repeated treatment of uncomplicated malaria in children under 5 years at Nagongera Health Centre, Uganda. Participants were randomized to ASAQ or AL and all subsequent malaria episodes were treated with the same regimen. 413 children were enrolled and experienced a total of 6027 malaria episodes (mean 15; range, 1–26). For the first malaria episode, the PCR-corrected-cure rate for ASAQ (97.5%) was non-inferior to that for AL (97.0%; 95% CI [−0.028; 0.037]). PCR-corrected cure rates for subsequent malaria episodes that had over 100 cases (episodes 2–18), ranged from 88.1% to 98.9% per episode, with no clear difference between the treatment arms. Parasites were completely cleared by day 3 for all malaria episodes and gametocyte carriage was less than 1% by day 21. Fever clearance was faster in the ASAQ group for the first episode. Treatment compliance for subsequent episodes (only first dose administration observed) was close to 100%. Adverse events though common were similar between treatment arms and mostly related to the disease. Serious adverse events were uncommon, comparable between treatment arms and resolved spontaneously. Anemia and neutropenia occurred in <0.5% of cases per episode, abnormal liver function tests occurred in 0.3% to 1.4% of cases. Both regimens were safe and effective for repeated treatment of malaria.</p><p>Trial Registration</p><p>Current Controlled Trials <a href="http://www.controlled-trials.com/mrct/trial/452497/NCT00699920" target="_blank">NCT00699920</a></p></div

Risk of recurrent parasitaemia.

<p>Survival curve showing cumulative risk of infection after PCR correction up to 28 days in the PP population.</p

Use of ITNs by study participants.

a<p>Question answered by investigator or an accompanying community healthcare worker.</p><p>Use of ITNs by study participants.</p

Incidence of AEs by episode.

<p>The incidence of AEs experienced per episode by children in the ASAQ and AL groups.</p

Malaria episodes experienced by patients during the 2 years of the study.

<p>(A) Number of children per malaria episode. (B) Number of children with malaria episodes during each month between June, 2008 and April, 2010.</p