Summary of findings 2. Pyronaridine‐artesunate (PY‐AS) compared to artesunate‐amodiaquine (AS‐AQ) for adults and children with uncomplicated Plasmodium falciparum malaria.
| Pyronaridine‐artesunate (PY‐AS) compared to artesunate‐amodiaquine (AS‐AQ) for adults and children with uncomplicated Plasmodium falciparum malaria | ||||||
| Patient or population: adults and children with uncomplicated P falciparum malaria Setting: malaria transmission settings Intervention: pyronaridine‐artesunate (PY‐AS) Comparison: artesunate‐amodiaquine (AS‐AQ) | ||||||
| Outcomesa | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (trials) | Certainty of the evidence (GRADE) | Comments | |
| Risk with artesunate‐amodiaquine (AS‐AQ) | Risk with pyronaridine‐artesunate (PY‐AS) | |||||
| Total failure: day 28 (PCR‐adjusted) | 8 per 1000 | 4 per 1000 (1 to 22) | RR 0.55 (0.11 to 2.77) | 1245 (1 RCT) | ⊕⊕⊝⊝
LOWb,c Due to indirectness and imprecision |
Compared to AS‐AQ, PY‐AS may have fewer PCR‐adjusted failures at day 28. |
| Total failure: day 42 (PCR‐adjusted) | 6 per 1000 | 5 per 1000 (1 to 27) | RR 0.98 (0.20 to 4.83) | 1091 (1 RCT) | ⊕⊕⊝⊝
LOWb,d Due to indirectness and imprecision |
There may be little or no difference in PCR‐adjusted failures at day 42 between PY‐AS and AS‐AQ. |
| Total failure: day 28 (unadjusted) | 75 per 1000 | 37 per 1000 (22 to 61) | RR 0.49 (0.30 to 0.81) | 1257 (1 RCT) | ⊕⊕⊕⊝
MODERATEb Due to indirectness |
Compared to AS‐AQ, PY‐AS probably has fewer unadjusted failures at day 28. |
| Total failure: day 42 (unadjusted) | 195 per 1000 | 192 per 1000 (152 to 240) | RR 0.98 (0.78 to 1.23) | 1235 (1 RCT) | ⊕⊕⊕⊝
MODERATEb Due to indirectness |
There is probably little or no difference in unadjusted failures at day 42 between PY‐AS and AS‐AQ. |
| First treatment, ALT increase > 5 × ULN (42 days) | 1 per 1000 | 1 per 1000 (0 to 7) | RR 1.41 (0.28 to 7.09) | 1317 (1 RCT) | ⊕⊕⊝⊝
LOWb,e Due to indirectness and imprecision |
Compared to AL, PY‐AS may have lead to higher events of ALT increase > 5 × ULN. (Aggregate analysis indicates this estimate may be accurate). |
| First treatment, AST increase > 5 × ULN (42 days) | 4 per 1000 | 2 per 1000 (0 to 8) | RR 0.43 (0.08 to 2.07) | 1317 (1 RCT) | ⊕⊝⊝⊝
VERY LOWb,f Due to indirectness and imprecision |
We do not know if there is a difference in AST between PY‐AS and AS‐AQ. |
| First treatment, bilirubin increase > 2.5 × ULN (42 days) | 1 per 1000 | 1 per 1000 (0 to 16) | RR 0.99 (0.06 to 15.76) | 1317 (1 RCT) | ⊕⊝⊝⊝
VERY LOWb,f Due to indirectness and imprecision |
We do not know if there is a difference in bilirubin between PY‐AS and AS‐AQ. |
| *The risk in the intervention group (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). Abbreviations: ALT: alanine aminotransferase; AS‐AQ: artesunate‐amodiaquine; AST: aspartate transaminase; CI: confidence interval; PCR: polymerase chain reaction; PY‐AS: pyronaridine‐artesunate; RCT: randomized controlled trial; RR: risk ratio; ULN: upper limit of normal | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect. | ||||||
aSerious adverse events data were not available disaggregated by site to allow inclusion in this comparison. bDowngraded by 1 for serious indirectness: the data are drawn from one study, conducted in six sites in three countries in West Africa. Further studies in Asia would be needed to fully apply this result. cDowngraded by 1 for serious imprecision: the CI is large and includes both no effect and clinically important effects. dDowngraded by 1 for serious imprecision: the effect estimate is close to no effect, but the CI is wide. eDowngraded by 1 for serious imprecision: the low number of events recorded in the study is insufficient for confidently estimating the effect size. However, aggregate analysis of ALT increase across different comparator drugs provides indirect evidence that the point estimate may be accurate. fDowngraded by 2 for very serious imprecision: the CI is very large and includes both no effect and clinically important effects.