Summary of findings 2.
Summary of findings table 2
| Artemether compared with quinine for treating adults with severe malaria | |||||
| Patient or population: Adults with severe malaria Settings: Malaria endemic countries Intervention: Intramuscular artemether Comparison: Intravenous or intramuscular quinine | |||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (trials) | Quality of the evidence (GRADE) | |
| Assumed risk | Corresponding risk | ||||
| Quinine | Artemether | ||||
| Death | 208 per 1000 | 123 per 1000 (87 to 173) | RR 0.59 (0.42 to 0.83) | 716 (4 trials) | ⊕⊕⊕⊝ moderate1,2,3,4 |
| Coma resolution time | ‐ | ‐ | Not pooled. Little difference. | 657 (2 trials) | ⊕⊕⊝⊝ low1,5,6, 7 |
| Neurological sequelae at discharge | 4 per 1000 |
12 per 1000 (1 to 111) |
RR 2.92 (0.31 to 27.86) | 560 (1 trial) | ⊕⊕⊝⊝ low7,8 |
| Parasite clearance time | ‐ | ‐ | Not pooled. Little difference apparent. | 716 (4 trials) | ⊕⊕⊕⊝ moderate1,3,6,9 |
| Fever clearance time | ‐ | ‐ | Not pooled. Little difference apparent. | 716 (4 trials) | ⊕⊕⊝⊝ low1,3,6,10 |
| *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 are generally well conducted and at low risk of bias. 2 No serious inconsistency: Statistically significant differences were only seen in one of the four trials. However, statistical heterogeneity between trials was low and the overall meta‐analysis is statistically significant. 3 No serious indirectness: All four trials compared intramuscular artemether with intravenous quinine in adults; two trials from Thailand, one each from Vietnam and Papua New Guinea 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. 5Hien 1996 VNM and Karbwang 1995 THA reported median coma time for artemether vs. quinine (Hien 1996 VNM: 66 vs. 48, P = 0.003; Karbwang 1995 THA: 48 vs. 48). Downgraded by 1 for inconsistency: One trial found a shorter median coma resolution time with quinine, and one trial found no difference. 6 Downgraded by 1 for imprecision: The data could not be pooled.
7 No serious risk of bias: This single trial was at low risk of bias.
8 Downgraded by 1 for serious imprecision: Neurological sequelae in adults were uncommon. This trial is underpowered to detect or exclude clinically important differences. 9 Two trials found no significant difference between parasite clearance time for artemether vs. quinine (Karbwang 1992 THA: mean 63.6 vs. 61.6, P = 0.85 and Seaton 1998 PNG: median 48 vs. 52, P = 0.381). Two other trials reported significantly shorter median parasite clearance times for artemether vs. quinine (Hien 1996 VNM: 72 vs. 90 P < 0.001 and Karbwang 1995 THA: 54 vs.78, P = 0.007). No serious inconsistency: The two largest trials both found shorter median clearance times with artemether. 10 Three trials (Hien 1996 VNM, Seaton 1998 PNG and Karbwang 1995 THA) reported median fever clearance time for artemether vs. quinine (127 vs. 90, P < 0.001; 32 vs. 48, P = 0.034 and 79 vs. 84, no significant difference). Karbwang 1992 THAreported mean fever clearance time and found a statistically significant reduction of about 30 hours with artemether. Downgraded by 1 for inconsistency: One trial found a shorter median fever clearance time with quinine, and two trials found a shorter time with artemether.