An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia

• Published in: PloS one Vol. 5; no. 7; p. e11880
• Main Authors: Valecha, Neena, Phyo, Aung Pyae, Mayxay, Mayfong, Newton, Paul N, Krudsood, Srivicha, Keomany, Sommay, Khanthavong, Maniphone, Pongvongsa, Tiengkham, Ruangveerayuth, Ronnatrai, Uthaisil, Chirapong, Ubben, David, Duparc, Stephan, Bacchieri, Antonella, Corsi, Marco, Rao, Bappanad H K, Bhattacharya, Prabash C, Dubhashi, Nagesh, Ghosh, Susanta K, Dev, Vas, Kumar, Ashwani, Pukrittayakamee, Sasithon, Pukittayakamee, Sasithon
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.07.2010; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Adults; Aged; Antimalarials - therapeutic use; Artemisinin; Artemisinins - therapeutic use; Artesunate; Asia; Child; Child, Preschool; Children; Clinical trials; Collaboration; Confidence intervals; Dihydroartemisinin; Drug dosages; Drug resistance; Erythrocytes; Female; Health aspects; Hospitals; Humans; Infant; Infection; Infectious Diseases/Neglected Tropical Diseases; Infectious Diseases/Protozoal Infections; Labels; Malaria; Malaria, Falciparum - drug therapy; Male; Medical research; Medicine; Medicine, Experimental; Mefloquine; Mefloquine - therapeutic use; Microbiology/Medical Microbiology; Middle Aged; Mixed infection; Motivation; Multidrug resistance; Parasites; Patients; Plasmodium falciparum; Polymerase chain reaction; Quinolines - therapeutic use; Randomization; Tropical diseases; Vector-borne diseases; Young Adult; Asia; Thailand; Laos; Bangkok Thailand; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0011880

The artemisinin-based combination treatment (ACT) of dihydroartemisinin (DHA) and piperaquine (PQP) is a promising novel anti-malarial drug effective against multi-drug resistant falciparum malaria. The aim of this study was to show non-inferiority of DHA/PQP vs. artesunate-mefloquine (AS+MQ) in Asia. This was an open-label, randomised, non-inferiority, 63-day follow-up study conducted in Thailand, Laos and India. Patients aged 3 months to 65 years with Plasmodium falciparum mono-infection or mixed infection were randomised with an allocation ratio of 2:1 to a fixed-dose DHA/PQP combination tablet (adults: 40 mg/320 mg; children: 20 mg/160 [DOSAGE ERROR CORRECTED] mg; n = 769) or loose combination of AS+MQ (AS: 50 mg, MQ: 250 mg; n = 381). The cumulative doses of study treatment over the 3 days were of about 6.75 mg/kg of DHA and 54 mg/kg of PQP and about 12 mg/kg of AS and 25 mg/kg of MQ. Doses were rounded up to the nearest half tablet. The primary endpoint was day-63 polymerase chain reaction (PCR) genotype-corrected cure rate. Results were 87.9% for DHA/PQP and 86.6% for AS+MQ in the intention-to-treat (ITT; 97.5% one-sided confidence interval, CI: >-2.87%), and 98.7% and 97.0%, respectively, in the per protocol population (97.5% CI: >-0.39%). No country effect was observed. Kaplan-Meier estimates of proportions of patients with new infections on day 63 (secondary endpoint) were significantly lower for DHA/PQP than AS+MQ: 22.7% versus 30.3% (p = 0.0042; ITT). Overall gametocyte prevalence (days 7 to 63; secondary endpoint), measured as person-gametocyte-weeks, was significantly higher for DHA/PQP than AS+MQ (10.15% versus 4.88%; p = 0.003; ITT). Fifteen serious adverse events were reported, 12 (1.6%) in DHA/PQP and three (0.8%) in AS+MQ, among which six (0.8%) were considered related to DHA/PQP and three (0.8%) to AS+MQ. DHA/PQP was a highly efficacious drug for P. falciparum malaria in areas where multidrug parasites are prevalent. The DHA/PQP combination can play an important role in the first-line treatment of uncomplicated falciparum malaria. Controlled-Trials.com ISRCTN81306618.