| Liver toxicity of pyronaridine compared to other antimalarials | |||||
| Patient or population: People with uncomplicated falciparum malaria Settings: High and low-transmission settings for P. falciparum and P. vivax malaria Intervention: Pyronaridine alone or with an artemisinin-derivative Comparison: Another antimalarial | |||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect(95% CI) | Number of participants(trials) | Quality of the evidence(GRADE) | |
| Assumed risk | Corresponding risk | ||||
| Comparator antimalarial | Pyronaridine alone or with artesunate | ||||
| Elevated alanine aminotransaminase levels Grade 3,4 toxicity | 2 per 1000 | 10 per 1000 (3 to 30) | RR 4.17 (1.38 to 12.61) | 3523(4 trials) | ⊕⊕⊕○ moderate 1,2,3,4 |
|
Elevated aspartate aminotransferase levels Grade 3, 4 toxicity |
2 per 1000 | 8 per 1000 (2 to 29) | RR 4.08 (1.17 to 14.26) | 3528(4 trials) | ⊕⊕⊕○ moderate 1,2,3,4 |
| Elevated alkaline phosphatase levels Grade 3, 4 toxicity | 2 per 1000 | 1 per 1000 (0 to 5) | RR 0.62 (0.15 to 2.51) | 2606(3 trials) | ⊕⊕⊕○ moderate 1,2,3,5 |
| Elevated bilirubin Grade 3, 4 toxicity | 3 per 1000 | 6 per 1000 (2 to 19) | RR 1.92 (0.59 to 6.24) | 3067(3 trials) | ⊕⊕○○low 1,2,3,6 |
| *The basis for the assumed risk (for example, the median control group risk across trials) is provided in footnotes. 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: Trials were well conducted, although the data analysis was not clearly independent of the drug manufacturer in three trials.
2 No serious inconsistency: Statistical heterogeneity was low.
3 Downgraded by one for serious indirectness: Only 232 children aged less than five years were included in these trials.
4 No serious imprecision: The 95% CI is wide, and there are few events. Larger trials would be necessary to have full confidence in this result but not downgraded.
5 No serious imprecision: The 95% CI is narrow and probably excludes clinically important differences.
6 Downgraded by one for serious imprecision: The 95% CI is wide and includes no difference and clinically important effects.