Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison

• Published in: The Lancet (British edition) 2007-03, Vol.369 (9563), p.757-765
• Main Authors: Ratcliff, A, FRACP, Siswantoro, H, MD, Kenangalem, E, MD, Maristela, R, MD, Wuwung, RM, Laihad, F, MD, Ebsworth, EP, MPH, Anstey, NM, Prof, Tjitra, E, MD, Price, RN, Dr
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anemia - etiology; Antimalarials - administration & dosage; Antimalarials - adverse effects; Artemether; Artemether, Lumefantrine Drug Combination; Artemisinin; Artemisinins - administration & dosage; Artemisinins - adverse effects; Artemisinins - therapeutic use; Biological and medical sciences; Child; Child, Preschool; Children & youth; Chloroquine; Clinics; Comparative studies; Diarrhea - chemically induced; Dihydroartemisinin; Drug Administration Schedule; Drug Combinations; Drug resistance; Drug Resistance, Multiple - drug effects; Drug therapy; Ethanolamines - therapeutic use; Ethics; Failure analysis; Female; Fluorenes - therapeutic use; Gametocytes; General aspects; Humans; Indonesia; Infant; Infections; Internal Medicine; Malaria; Malaria, Falciparum - complications; Malaria, Falciparum - drug therapy; Malaria, Vivax - complications; Malaria, Vivax - drug therapy; Male; Medical research; Medical sciences; Middle Aged; Motivation; Multidrug resistance; Patients; Prophylaxis; Prospective Studies; Public health; Quinolines - administration & dosage; Quinolines - adverse effects; Recurrence; Risk; Sesquiterpenes - administration & dosage; Sesquiterpenes - adverse effects; Treatment Outcome; Urticaria - chemically induced; Vector-borne diseases; Vomiting - chemically induced
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(07)60160-3

Summary Background The burden of Plasmodium vivax infections has been underappreciated, especially in southeast Asia where chloroquine resistant strains have emerged. Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax. Methods 774 patients in southern Papua, Indonesia, with slide-confirmed malaria were randomly assigned to receive either artemether-lumefantrine or dihydroartemisinin-piperaquine and followed up for at least 42 days. The primary endpoint was the overall cumulative risk of parasitological failure at day 42 with a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov , trial number 00157833. Findings Of the 754 evaluable patients enrolled, 466 had infections with P falciparum , 175 with P vivax , and 113 with a mixture of both species. The overall risk of failure at day 42 was 43% (95% CI 38–48) for artemether-lumefantrine and 19% (14–23) for dihydroartemisinin-piperaquine (hazard ratio=3·0, 95% CI 2·2–4·1, p