Abstract | BACKGROUND: METHODS: Individual patient data on safety outcomes were integrated from six randomized clinical trials conducted in Africa and Asia in patients with microscopically confirmed P. falciparum (five studies) or P. vivax (one study) malaria. Efficacy against P. falciparum was evaluated across three Phase III clinical trials. RESULTS: The safety population included 2,815 patients randomized to PA, 1,254 to comparators: mefloquine + artesunate (MQ + AS), artemether-lumefantrine (AL), or chloroquine. All treatments were generally well tolerated. Adverse events occurred in 57.2% (1,611/2,815) of patients with PA versus 51.5% (646/1,254) for comparators, most commonly (PA; comparators): headache (10.6%; 9.9%), cough (5.9%; 5.6%) and anaemia (4.5%; 2.9%). Serious averse events were uncommon for all treatments (0-0.7%). Transient increases in alanine aminotransferase and aspartate aminotransferase were observed with PA but did not lead to any clinical sequelae. For P. falciparum malaria, day-28 PCR-corrected adequate clinical and parasitological response with PA was 93.6% ([1,921/2,052] 95% CI 92.6, 94.7) in the intent-to-treat population and 98.5% ([1,852/1,880] 95% CI 98.0, 99.1) in the per-protocol population. Median parasite clearance time was 24.1 h with PA, 31.9 h with MQ + AS, and 24.0 h with AL. Median fever clearance time was 15.5 h with PA, 15.8 h with MQ + AS, and 14.0 h with AL. By day 42, P. falciparum gametocytes had declined to near zero for all treatments. CONCLUSIONS: TRIAL REGISTRATION: Clinicaltrials.gov: NCT00331136; NCT00403260; NCT00422084; NCT00440999; NCT00541385; NCT01594931.
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Authors | Stephan Duparc, Isabelle Borghini-Fuhrer, Carl J Craft, Sarah Arbe-Barnes, Robert M Miller, Chang-Sik Shin, Lawrence Fleckenstein |
Journal | Malaria journal
(Malar J)
Vol. 12
Pg. 70
(Feb 21 2013)
ISSN: 1475-2875 [Electronic] England |
PMID | 23433102
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimalarials
- Artemisinins
- Drug Combinations
- Naphthyridines
- Artesunate
- pyronaridine
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Topics |
- Adolescent
- Adult
- Africa
- Antimalarials
(administration & dosage, adverse effects)
- Artemisinins
(administration & dosage, adverse effects)
- Artesunate
- Asia
- Child
- Child, Preschool
- Clinical Trials, Phase III as Topic
- Drug Combinations
- Drug-Related Side Effects and Adverse Reactions
(epidemiology)
- Female
- Humans
- Infant
- Malaria
(drug therapy)
- Malaria, Falciparum
(drug therapy)
- Malaria, Vivax
(drug therapy)
- Male
- Middle Aged
- Naphthyridines
(administration & dosage, adverse effects)
- Randomized Controlled Trials as Topic
- Treatment Outcome
- Young Adult
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