2.
| Artesunate compared with quinine for treating severe malaria | ||||||
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Patient or population: Adults with severe malaria Settings: Malaria endemic areas Intervention: Artesunate Comparison: Quinine | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of Participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Quinine | Artesunate | |||||
| Death | 241 per 1000 | 147 per 1000 (121 to 181) | RR 0.61 (0.5 to 0.75) | 1664 (5 studies1) | high2,3,4,5 | |
| Neurological sequelae at day 28 | ‐ | ‐ | ‐ | ‐ | ‐ | Not reported |
| Neurological sequelae at discharge | 3 per 1000 | 9 per 1000 (2 to 44) | RR 2.97 (0.6 to 14.64) | 1259 (1 study6) | moderate7,8,9,10 | |
| Time to hospital discharge (days) | See comment | See comment | Not estimable | 113 (2 studies11) | moderate12,13,14,15 | |
| Hypoglycaemia episodes | 47 per 1000 | 17 per 1000 (9 to 32) | RR 0.36 (0.19 to 0.68) | 1372 (2 studies11) | high12,16,14,17 | |
| *The assumed risk was calculated by dividing the total number of events in the control group (across studies) by the total number of patients in the control group (across studies). This was numerically very similar to the median control group risk but is easier to link with the corresponding forest plot. 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 One large multicentre trial (Dondorp 2005) and four smaller trials (Anh 1989, Anh 1995, Hien 1992, Newton 2003) have assessed artesunate vs quinine in adults 2 No serious study limitations: two of the smaller studies did not conceal allocation and none of the studies were blinded. However the majority of the data is from studies which did conceal allocation and the lack of blinding is unlikely to introduce bias for an objective outcome such as death. 3 No serious inconsistency: The point estimates of all five trials favoured artesunate. No significant statistical heterogeneity was detected (I² = 0%). 4 No serious indirectness: All five trials were from Asia, but from a variety of settings (Vietnam, Bangladesh, India, Myanmar, Indonesia and Thailand), and included age groups above 15/16 years. Of the four small trials; two did not give the loading dose of quinine, but there was no statistical heterogeneity between these two trials and the large multicentre trial which did give the loading dose. 5 No serious imprecision: Both limits of the 95% CI imply a clinically important benefit with artesunate. 6 Only one trial reported the incidence of neurological sequelae in adults (Dondorp 2005). This is unpublished data received from the authors. 7 No serious study limitations: This trial was unblinded but the nature of the sequelae makes an observer or reporting bias unlikely 8 No serious inconsistency: Not applicable as only one trial 9 No serious indirectness: This trial had sites in four different countries in Asia and used the established standard doses of artesunate and quinine (with loading dose). Of the 10 sequelae which occurred in this trial (the additional two were in children): Five were psychiatric sequelae, four were a persistent problem with balance, and two had a hemiparesis. 10 Serious imprecision: Neurological sequelae appear to be a rare event following severe malaria in adults. However the 95% CI includes the possibility of a clinically important harm with artesunate. 11 Two trials (Dondorp 2005 and Newton 2003) report this outcome. 12 No serious study limitations: Dondorp 2005 adequately concealed allocation to be considered at low risk of bias, Newton 2003 did not but is a much smaller trial. Neither trial was blinded 13 No serious inconsistency: Neither trial found a statistically significant difference in time to hospital discharge 14 No serious indirectness: This evidence is from multiple sites within Asia (Bangladesh, India, Myanmarand Indonesia) and both trials used standard drug doses. The data from Dondorp 2005 does include some children. 15 Serious imprecision: We were unable to pool data due to the way data were presented but there is no evidence of a benefit on this outcome with artesunate. 16 No serious inconsistency: There was no statistical heterogeneity (I² = 0%) 17 No serious imprecision: This result is statistically significant in favour of artesunate. The current sample size is adequately powered to detect a 75% risk reduction with 80% power and 95% confidence.