Muhindo Mavoko H., Nabasumba C., Tinto H., D'Alessandro U., Grobusch M.P., Lutumba P., Van Geertruyden J.-P.
Département de Médecine Tropicale, Faculté de Médecine, Université de Kinshasa, B.P. 747 Kin XI, Democratic Republic Congo; Epicentre Mbarara Reasearch Base, P. O. Box 930, Mbarara, Uganda; Centre Muraz, Institut de Recherche en Sciences de la Santé, P. O. Box 545, Bobo Dioulasso, Burkina Faso; Institute of Tropical Medicine, Nationalestraat 155, B-2000, Antwerp, Belgium; Medical Research Council, The Gambia Unit, P. O. Box 273, Banjul, Gambia; Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands; International Health Unit, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610, Wilrijk, Belgium
Muhindo Mavoko, H., Département de Médecine Tropicale, Faculté de Médecine, Université de Kinshasa, B.P. 747 Kin XI, Democratic Republic Congo; Nabasumba, C., Epicentre Mbarara Reasearch Base, P. O. Box 930, Mbarara, Uganda; Tinto, H., Centre Muraz, Institut de Recherche en Sciences de la Santé, P. O. Box 545, Bobo Dioulasso, Burkina Faso; D'Alessandro, U., Institute of Tropical Medicine, Nationalestraat 155, B-2000, Antwerp, Belgium, Medical Research Council, The Gambia Unit, P. O. Box 273, Banjul, Gambia; Grobusch, M.P., Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands; Lutumba, P., Département de Médecine Tropicale, Faculté de Médecine, Université de Kinshasa, B.P. 747 Kin XI, Democratic Republic Congo; Van Geertruyden, J.-P., International Health Unit, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610, Wilrijk, Belgium
Background: Artemisinin-based combination therapy is currently recommended by the World Health Organization as first-line treatment of uncomplicated malaria. Recommendations were adapted in 2010 regarding rescue treatment in case of treatment failure. Instead of quinine monotherapy, it should be combined with an antibiotic with antimalarial properties; alternatively, another artemisinin-based combination therapy may be used. However, for informing these policy changes, no clear evidence is yet available. The need to provide the policy makers with hard data on the appropriate rescue therapy is obvious. We hypothesize that the efficacy of the same artemisinin-based combination therapy used as rescue treatment is as efficacious as quinine + clindamycin or an alternative artemisinin-based combination therapy, without the risk of selecting drug resistant strains.Design: We embed a randomized, open label, three-arm clinical trial in a longitudinal cohort design following up children with uncomplicated malaria until they are malaria parasite free for 4 weeks. The study is conducted in both the Democratic Republic of Congo and Uganda and performed in three steps. In the first step, the pre-randomized controlled trial (RCT) phase, children aged 12 to 59 months with uncomplicated malaria are treated with the recommended first-line drug and constitute a cohort that is passively followed up for 42 days. If the patients experience an uncomplicated malaria episode between days 14 and 42 of follow-up, they are randomized either to quinine + clindamycin, or an alternative artemisinin-based combination therapy, or the same first-line artemisinin-based combination therapy to be followed up for 28 additional days. If between days 14 and 28 the patients experience a recurrent parasitemia, they are retreated with the recommended first-line regimen and actively followed up for another 28 additional days (step three; post-RCT phase). The same methodology is followed for each subsequent failure. In any case, all patients without an infection at day 28 are classified as treatment successes and reach a study endpoint. The RCT phase allows the comparison of the safety and efficacy of three rescue treatments. The prolonged follow-up of all children until they are 28 days parasite-free allows us to assess epidemiological-, host- and parasite-related predictors for repeated malaria infection.Trial registration: NCT01374581 and PACTR201203000351114. © 2013 Muhindo Mavoko et al.; licensee BioMed Central Ltd.
amodiaquine plus artesunate; artemether plus benflumetol; clindamycin; co arsucam; doxycycline; hemoglobin; quinamax; quinine; tetracycline; unclassified drug; winthrop; adverse outcome; article; body weight; child; childhood disease; clinical protocol; cohort analysis; Congo; controlled study; drug comparison; drug efficacy; drug safety; drug treatment failure; female; fever; follow up; genotype; hematological parameters; hemoglobin blood level; hospitalization; human; hypothesis; insurance; liver function; longitudinal study; major clinical study; malaria; malaria falciparum; male; monotherapy; multicenter study; multidrug resistance; open study; outcome assessment; parasite clearance; parasite incidence; parasitemia; pharmacoepidemiology; phase 3 clinical trial; Plasmodium; preschool child; randomized controlled trial; recurrent infection; reinfection; retreatment; treatment duration; tympanic temperature; Uganda; unspecified side effect; world health organization; Amodiaquine; Antimalarials; Artemisinins; Child, Preschool; Clindamycin; Clinical Protocols; Democratic Republic of the Congo; Drug Combinations; Drug Resistance; Drug Therapy, Combination; Ethanolamines; Female; Fluorenes; Humans; Incidence; Infant; Longitudinal Studies; Malaria, Falciparum; Male; Plasmodium falciparum; Quinine; Recurrence; Research Design; Retreatment; Time Factors; Treatment Outcome; Uganda