Summary of findings 3.
Artemether compared with artesunate for treating adults with severe malaria | |||||
Patient or population: Adults with severe malaria Settings: Malaria endemic countries Intervention: Intramuscular artemether Comparison: Intravenous or intramuscular artesunate | |||||
Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (trials) | Quality of the evidence (GRADE) | |
Assumed risk | Corresponding risk | ||||
Artesunate | Artemether | ||||
Death | 87 per 1000 | 156 per 1000 (95 to 258) | RR 1.80 (1.09 to 2.97) | 494 (2 trials) | ⊕⊕⊕⊝ moderate1,2,3,4 |
Coma resolution time | ‐ | ‐ | Not pooled. No significant difference | 494 (2 trials) | ⊕⊕⊕⊝ moderate1,3,5,6 |
Neurological sequelae at discharge | ‐ | ‐ | ‐ | 0 (0 trials) | ‐ |
Parasite clearance time | ‐ | ‐ | Not pooled. No significant difference | 494 (2 trials) | ⊕⊕⊕⊝ moderate1,3,6,7 |
Fever clearance time | ‐ | ‐ | Not pooled. No significant difference | 494 (2 trials) | ⊕⊕⊝⊝ low1,3,6,8 |
*The assumed risk is the median control group risk across studies. 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 generally well conducted and at low risk of bias. 2 No serious inconsistency: There is no statistical heterogeneity 3 No serious indirectness: The two trials were conducted in Vietnam and Thailand and both compared intramuscular artemether with intravenous artesunate in adults. 4 Downgraded by 1 for serious imprecision: These trials, and the overall meta‐analysis are very underpowered to detect a difference in mortality or to prove equivalence. 5Phu 2010 VNM and Vinh 1997 VNM reported median coma resolution time for artemether vs. artesunate (Phu 2010 VNM: 72 vs. 60, P = 0.11; Vinh 1997 VNM: 47 (artemether) vs. 30 (artesunate IM) vs. 24 (artesunate IV). No serious inconsistency: Both trials suggest an advantage with artesunate although not statistically significant. 6 Downgraded by 1 for serious imprecision: We could not pool these data as median data were presented for both trials. 7Phu 2010 VNM and Vinh 1997 VNM reported median parasite clearance time (Phu 2010 VNM: 72 vs. 72, P = 0.97; Vinh 1997 VNM: 30 (artemether) vs. 24 (artesunate IM) vs. 24 (artesunate IV). No serious inconsistency: Both trials found no difference between treatments. 8Phu 2010 VNM and Vinh 1997 VNM reported median fever clearance time (Phu 2010 VNM: 108 vs. 108, P = 0.27; Vinh 1997 VNM: 48 (artemether) vs. 36 (artesunate IM) vs. 30 (artesunate IV). No serious inconsistency: Both trials found no statistically significant difference between artemether and artesunate.