| Artesunate-pyronaridine compared to artemether-lumefantrine for treating people with uncomplicated falciparum malaria | |||||
| Patient or population: Adults and children with uncomplicated falciparum malaria Settings: Malaria endemic areas in Africa and Asia Intervention: Artesunate-pyronaridine Comparison: Artemether-lumefantrine | |||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect(95% CI) | No of participants(trials) | Quality of the evidence(GRADE) | |
| Assumed risk | Corresponding risk | ||||
| Artemether-lumefantrine | Artesunate-pyronaridine | ||||
| Treatment failure (day 28) | PCR-unadjusted | RR 0.60 (0.40 to 0.90) | 1720(2 trials) | ⊕⊕⊕○ moderate 1,2,3,4 | |
| 7 per 100 | 4 per 100 (3 to 6) | ||||
| PCR-adjusted | RR 1.69 (0.56 to 5.10) | 1650(2 trials) | ⊕⊕⊕○ moderate 1,2,3,5 | ||
| 1 per 100 | 1 per 100 (0 to 4) | ||||
| Treatment failure (Day 42) | PCR-unadjusted | RR 0.85 (0.53 to 1.36) | 1691 (2 trials) |
⊕⊕⊕○ moderate 1,2,3,5 | |
| 17 per 100 | 15 per 100 (9 to 23) | ||||
| PCR-adjusted | RR 1.53 (0.73 to 3.19) | 1472(2 trials) | ⊕⊕○○low 1,6,3,5 | ||
| 2 per 100 | 3 per 100 (1 to 6) | ||||
| The assumed risk is the mean risk across the trials in those treated with artemether-lumefantrine. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio. | |||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | |||||
1 No serious risk of bias: Both trials were well conducted and at low risk of bias.
2 No serious inconsistency: The trend was towards benefit with artesunate-pyronaridine in both trials but only reached statistical significance in one.
3 Downgraded by one for serious indirectness: The two trials were conducted in children aged between three months and 12 years and had trial sites in Africa and Asia. However across both trials only 152 children aged < five years received artesunate-pyronaridine, and only 115 children in total were randomized to artesunate-pyronaridine in Asia. Further adequately powered studies in children in Africa and adults and children in Asia would be needed to fully generalize this result.
4 No serious imprecision: The result is statistically significant and the meta-analysis is adequately powered. However, it should be noted that these multicentred trials are underpowered to show equivalence at the country level. We did not downgrade.
5 No serious imprecision: The finding is of no substantial difference between the two ACTs. However, it should it should be noted that these multicentred trials are underpowered to show equivalence at the country level. We did not downgrade.
6 Downgraded by one for serious inconsistency: Although statistical heterogeneity was low, PCR-adjusted treatment failure was above 5% in on the one trial recruiting children aged < five years.
7 For adverse events see the additional Summary of Findings table in Appendix 2.