Intermittent preventive treatment: efficacy and safety of sulfadoxine-pyrimethamine and sulfadoxine-pyrimethamine plus piperaquine regimens in schoolchildren of the Democratic Republic of Congo: a study protocol for a randomized controlled trial

BACKGROUND In malaria endemic areas, schoolchildren usually have asymptomatic malaria infections and consequently remain untreated. Therefore, intermittent preventive treatment with sulfadoxine-pyrimethamine in schoolchildren would be a plausible strategy in malaria stable transmission areas to prevent anaemia and malnutrition. However, in contrast to infancy and pregnancy, antimalaria intermittent preventive treatment in children has been barely investigated. As the implementation of intermittent preventive treatment may be challenged by sulfadoxine-pyrimethamine resistance, sulfadoxine-pyrimethamine combined with piperaquine may be a better alternative than sulfadoxine-pyrimethamine monotherapy. A clinical trial is being conducted to assess the efficacy and safety of intermittent preventive treatments versus controls in Democratic Republic of Congo (DRCongo) schoolchildren and their impact on sulfadoxine-pyrimethamine resistance. METHODS/DESIGN A phase IIIb, randomised, controlled trial will enroll asymptomatic schoolchildren. For interventions, sulfadoxine-pyrimethamine is compared to sulfadoxine-pyrimethamine plus piperaquine and to a control group. The two treatments are given four-monthly from baseline for a year as a single dose for sulfadoxine-pyrimethamine and two doses at 24-hour intervals for piperaquine. All participants receive praziquantel and albendazole as mass-treatment for helminthiasis at enrolment. The primary endpoint is haemoglobin concentration change at 12 months follow-up. Secondary endpoints are malaria parasite load and malaria prevalence, at baseline and at month 12. Malaria and helminthiasis incidence will be monitored throughout the study. Statistical analysis will use multilevel modelling due to repeated measurements and clustering effect of participants. DISCUSSION The very few studies on intermittent preventive treatment in schoolchildren in malaria stable transmission areas have contradictory results. This randomised controlled trial is unique in comparing efficacy and safety of a prophylactic combination therapy to monotherapy or a control group after 12 months follow-up. Resistance markers for sulfadoxine-pyrimethamine (including break through parasitaemias) will also be recorded. Its uniqueness lies also in the fact that we use piperaquine, a long acting antimalarial, in combination with sulfadoxine-pyrimethamine. Artemisinin derivatives have been excluded as it is part of the treatment policies in virtually all malaria endemic countries. Our findings may, therefore, contribute to the public health of youngsters who fail to thrive and grow due to multiple morbidities. TRIAL REGISTRATION NCT01722539; PACTR201211000449323.