for the main comparison.
| Artesunate compared with quinine for treating severe malaria | ||||||
|
Patient or population: Children 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 | 109 per 1000 | 83 per 1000 (71 to 98) | RR 0.76 (0.65 to 0.9) | 5765 (4 studies1) | high2,3,4,5 | |
| Neurological sequelae at day 28 | 11 per 1000 | 14 per 1000 (8 to 22) | RR 1.23 (0.74 to 2.03) | 4857 (1 study6) | moderate7,8,9,10 | |
| Neurological sequelae at discharge | 28 per 1000 | 38 per 1000 (28 to 51) | RR 1.36 (1.01 to 1.83) | 5163 (3 studies11) | moderate2,3,4,12 | |
| Time to hospital discharge (days) | See comment | See comment | Not estimable | 113 (3 studies11) | moderate2,13,4,14 | |
| Hypoglycaemia episodes | 30 per 1000 | 19 per 1000 (13 to 26) | RR 0.62 (0.45 to 0.87) | 5765 (4 studies1) | high2,3,4,15 | |
| *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 2010) and two small trials (Cao 1997, Eltahir 2010) have assessed artesunate vs quinine in children aged < 15 years. In addition one large multicentre study included a subgroup of children in this age group (Dondorp 2005) 2 No serious study limitations: All the trials adequately concealed allocation to be considered at low risk of bias. The trials were unblinded but this is unlikely to bias this objective outcome 3 No serious inconsistency: There was no statistical heterogeneity between the trials (I² = 0%). 4 No serious indirectness: Most of the data is from Dondorp 2010 which had centres in Mozambique, the Gambia, Ghana, Kenya, Tanzania, Nigeria, Uganda, Rwanda and the Democratic Republic of Congo, and used the established standard doses of artesunate and quinine (with loading dose). Of note the median age of children in this trial was 2.9 years in the quinine group and 2.8 in the artesunate group. 5 No serious imprecision: Both limits of the 95% CI of the pooled effect imply an appreciable clinical benefit with artesunate. The Number Needed To Treat to prevent one childhood death is 38. 6 Only one large multicentre trial (Dondorp 2010) reports this outcome. 7 Serious study limitations: 41/170 (24%) patients with neurological sequelae at discharge were not available for assessment at day 28. 8 No serious inconsistency: Not applicable as only one trial. 9 No serious indirectness: This trial (Dondorp 2010) had 11 centres throughout Africa and used the standard dosing of artesunate and quinine. The nature of the neurological sequelae is not described. 10 No serious Imprecision: The 95% CI around the absolute effect is narrow. The worst case scenario is a 1.2% increase in neurological sequelae at day 28 11 Three trials (Dondorp 2010, Dondorp 2005, and Cao 1997) report this outcome 12 Serious imprecision: The effect estimate is of a clinically important harm. However the 95% CI includes the possibility of no clinically important difference between the two interventions. 13 No serious inconsistency: None of the trials found evidence of an important difference between the two treatment groups 14 Serious imprecision: We were unable to pool the data as they were only reported as medians and range/intra quartile range. There is no evidence of a clinically important benefit with artesunate on this outcome. 15 No serious imprecision: The result is statistically significant in favour of artesunate. The current sample size is adequately powered to detect a 40% risk reduction with 80% power and 95% confidence.