OBJECTIVES: Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RR) and continuous data using mean differences (MD), and presented all results with a 95% confidence interval (CI). We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS: We included six randomized controlled trials enrolling 3718 children and adults.
Artesunate-
pyronaridine versus
artemether-lumefantrineIn two multicentre trials, enrolling mainly older children and adults from west and south-central Africa, both
artesunate-
pyronaridine and
artemether-lumefantrine had fewer than 5% PCR adjusted treatment failures during 42 days of follow-up, with no differences between groups (two trials, 1472 participants, low quality evidence). There were fewer new
infections during the first 28 days in those given
artesunate-
pyronaridine (PCR-unadjusted treatment failure: RR 0.60, 95% CI 0.40 to 0.90, two trials, 1720 participants, moderate quality evidence), but no difference was detected over the whole 42 day follow-up (two trials, 1691 participants, moderate quality evidence).
Artesunate-
pyronaridine versus
artesunate plus mefloquineIn one multicentre trial, enrolling mainly older children and adults from South East Asia, both
artesunate-
pyronaridine and
artesunate plus
mefloquine had fewer than 5% PCR adjusted treatment failures during 28 days follow-up (one trial, 1187 participants, moderate quality evidence). PCR-adjusted treatment failures were 6% by day 42 for these treated with
artesunate-
pyronaridine, and 4% for those with
artesunate-
mefloquine (RR 1.64, 95% CI 0.89 to 3.00, one trial, 1116 participants, low quality evidence). Again, there were fewer new
infections during the first 28 days in those given
artesunate-
pyronaridine (PCR-unadjusted treatment failure: RR 0.35, 95% CI 0.17 to 0.73, one trial, 1720 participants, moderate quality evidence), but no differences were detected over the whole 42 days (one trial, 1146 participants, low quality evidence). Adverse effectsSerious adverse events were uncommon in these trials, with no difference detected between
artesunate-
pyronaridine and comparator ACTs. The analysis of liver function tests showed biochemical elevation were four times more frequent with
artesunate-
pyronaridine than with the other
antimalarials (RR 4.17, 95% CI 1.38 to 12.62, four trials, 3523 participants, moderate quality evidence).
AUTHORS' CONCLUSIONS: