Cochrane · systematic review · CD006404
Pyronaridine‐artesunate for treating uncomplicated Plasmodium falciparum malaria
Pryce, J, Taylor, M, Fox, T, et al. · Cochrane Database of Systematic Reviews · 2022 · Cochrane Library
SoF tableOnly the outcomes this review put in its Summary of Findings table are listed (the Cochrane Handbook caps them at about seven per comparison). Its other analyses are not shown here.
Questions
32
current version
GRADE rated
30
No studies
2
Included studies
NR
No studies 2 · 6.3%Ungraded 0 · 0%Very low 4 · 12.5%Low 19 · 59.4%Moderate 6 · 18.8%High 1 · 3.1%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Questions and results
Current version onlyPyronaridine‐artesunate (PY‐AS) compared to artemether‐lumefantrine (AL) for adults and children with uncomplicated Plasmodium falciparum malaria
Population: adults and children with uncomplicated P falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total failure: day 28 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.59 [0.26, 1.31] | 4 studies · 3068 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Total failure: day 42 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.86 [0.49, 1.51] | 4 studies · 2575 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Total failure: day 28 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.27 [0.13, 0.58] | 4 studies · 3149 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Total failure: day 42 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.61 [0.46, 0.82] | 4 studies · 3080 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Serious adverse events (42 days) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 1.16 [0.3, 4.5] | 3 studies · 2004 participants | Low Downgraded: imprecision, inconsistency |
First treatment, abnormal ALT increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 3.34 [1.33, 8.39] | 4 studies · 3415 participants | Low Downgraded: imprecision, inconsistency, indirectness |
First treatment, abnormal AST increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 3.12 [1.23, 7.94] | 4 studies · 3415 participants | Low Downgraded: imprecision, inconsistency, indirectness |
First treatment, abnormal bilirubin increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.82 [0.33, 2.04] | 3 studies · 3130 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Pyronaridine‐artesunate (PY‐AS) compared to artesunate‐amodiaquine (AS‐AQ) for adults and children with uncomplicated Plasmodium falciparum malaria
Population: adults and children with uncomplicated P falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcomesa Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | no estimate extracted | NR | No studies |
Total failure: day 28 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.55 [0.11, 2.77] | 1 study · 1245 participants | Low Downgraded: imprecision, indirectness |
Total failure: day 42 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.98 [0.2, 4.83] | 1 study · 1091 participants | Low Downgraded: imprecision, indirectness |
Total failure: day 28 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.49 [0.3, 0.81] | 1 study · 1257 participants | Moderate Downgraded: imprecision, indirectness |
Total failure: day 42 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.98 [0.78, 1.23] | 1 study · 1235 participants | Moderate Downgraded: imprecision, indirectness |
First treatment, abnormal ALT increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 1.41 [0.28, 7.09] | 1 study · 1317 participants | Low Downgraded: imprecision, indirectness |
First treatment, abnormal AST increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.4 [0.08, 2.07] | 1 study · 1317 participants | Very low Downgraded: imprecision, indirectness |
First treatment, abnormal bilirubin increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.99 [0.06, 15.76] | 1 study · 1317 participants | Very low Downgraded: imprecision, indirectness |
Pyronaridine‐artesunate (PY‐AS) compared to mefloquine plus artesunate (MQ + AS) for adults and children with uncomplicated Plasmodium falciparum malaria
Population: adults and children with uncomplicated P falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total failure: day 28 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ + AS) | RR 0.37 [0.13, 1.05] | 1 study · 1117 participants | Low Downgraded: imprecision, indirectness |
Total failure: day 42 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ + AS) | RR 1.8 [0.9, 3.57] | 1 study · 1037 participants | Low Downgraded: imprecision, indirectness |
Total failure: day 28 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ + AS) | RR 0.36 [0.17, 0.78] | 1 study · 1120 participants | Moderate Downgraded: imprecision, indirectness |
Total failure: day 42 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ + AS) | RR 0.84 [0.54, 1.31] | 1 study · 1059 participants | Low Downgraded: imprecision, indirectness |
Serious adverse events (42 days) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ + AS) | RR 1 [0.25, 3.97] | 1 study · 1271 participants | Low Downgraded: imprecision, indirectness |
First treatment, abnormal ALT increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ + AS) | RR 7.48 [0.99, 56.45] | 1 study · 1271 participants | Low Downgraded: imprecision, indirectness |
First treatment, abnormal AST increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ + AS) | RR 9.49 [0.55, 162.64] | 1 study · 1271 participants | Very low Downgraded: imprecision, indirectness |
First treatment, abnormal bilirubin increase (42 days) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ + AS) | RR 3.49 [0.43, 28.29] | 1 study · 1271 participants | Very low Downgraded: imprecision, indirectness |
Pyronaridine‐artesunate (PY‐AS) compared to other antimalarials for adults and children with uncomplicated malaria
Population: adults and children with uncomplicated malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcomesa,b,c Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | no estimate extracted | NR | No studies |
Serious adverse events Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.24 [0.54, 2.84] | 7 studies · 3941 participants | Moderate Downgraded: imprecision |
First treatment, abnormal ALT increase Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 3.59 [1.76, 7.33] | 8 studies · 6669 participants | High |
First treatment, abnormal AST increase Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 2.22 [1.12, 4.41] | 8 studies · 6669 participants | Moderate Downgraded: imprecision |
First treatment, abnormal bilirubin increase Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.03 [0.49, 2.18] | 7 studies · 6384 participants | Moderate Downgraded: imprecision |
Subsequent treatment(s), abnormal ALT increase Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 2.18 [0.76, 6.27] | 1 study · 1649 participants | Low Downgraded: imprecision, indirectness |
Subsequent treatment(s), abnormal AST increase Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.82 [0.74, 4.44] | 1 study · 1649 participants | Low Downgraded: imprecision, indirectness |
Subsequent treatment(s), abnormal bilirubin increase Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.13 [0.42, 3.01] | 1 study · 1649 participants | Low Downgraded: imprecision, indirectness |
Pyronaridine‐artesunate (PY‐AS) compared to artemether‐lumefantrine (AL) for adults and children with uncomplicated Plasmodium falciparum malaria
Population: adults and children with uncomplicated P falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total failure: day 28 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.59 [0.26, 1.31] | 4 studies · 3068 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Total failure: day 42 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.86 [0.49, 1.51] | 4 studies · 2575 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Total failure: day 28 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.27 [0.13, 0.58] | 4 studies · 3149 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Total failure: day 42 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.61 [0.46, 0.82] | 4 studies · 3080 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Serious adverse events (42 days) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.9 [0.19, 4.22] | 3 studies · 2004 participants | Low Downgraded: imprecision, inconsistency |
First treatment, ALT increase > 5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 2.92 [1.15, 7.41] | 4 studies · 3341 participants | Low Downgraded: imprecision, inconsistency, indirectness |
First treatment, AST increase > 5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 2.2 [0.83, 5.82] | 4 studies · 3327 participants | Very low Downgraded: imprecision, inconsistency, indirectness |
First treatment, bilirubin increase > 2.5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs artemether‐lumefantrine (AL) | RR 0.82 [0.33, 2.04] | 3 studies · 3130 participants | Low Downgraded: imprecision, inconsistency, indirectness |
Pyronaridine‐artesunate (PY‐AS) compared to artesunate‐amodiaquine (AS‐AQ) for adults and children with uncomplicated Plasmodium falciparum malaria
Population: adults and children with uncomplicated P falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcomesa Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | no estimate extracted | NR | No studies |
Total failure: day 28 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.55 [0.11, 2.77] | 1 study · 1245 participants | Low Downgraded: imprecision, indirectness |
Total failure: day 42 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.98 [0.2, 4.83] | 1 study · 1091 participants | Low Downgraded: imprecision, indirectness |
Total failure: day 28 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.49 [0.3, 0.81] | 1 study · 1257 participants | Moderate Downgraded: imprecision, indirectness |
Total failure: day 42 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.98 [0.78, 1.23] | 1 study · 1235 participants | Moderate Downgraded: imprecision, indirectness |
First treatment, ALT increase > 5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 1.41 [0.28, 7.09] | 1 study · 1317 participants | Low Downgraded: imprecision, indirectness |
First treatment, AST increase > 5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.43 [0.08, 2.07] | 1 study · 1317 participants | Very low Downgraded: imprecision, indirectness |
First treatment, bilirubin increase > 2.5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs artesunate‐amodiaquine (AS‐AQ) | RR 0.99 [0.06, 15.76] | 1 study · 1317 participants | Very low Downgraded: imprecision, indirectness |
Pyronaridine‐artesunate (PY‐AS) compared to mefloquine plus artesunate (MQ+AS) for adults and children with uncomplicated Plasmodium falciparum malaria
Population: adults and children with uncomplicated P falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total failure: day 28 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ+AS) | RR 0.37 [0.13, 1.05] | 1 study · 1117 participants | Low Downgraded: imprecision, indirectness |
Total failure: day 42 (PCR‐adjusted) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ+AS) | RR 1.8 [0.9, 3.57] | 1 study · 1037 participants | Low Downgraded: imprecision, indirectness |
Total failure: day 28 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ+AS) | RR 0.36 [0.17, 0.78] | 1 study · 1120 participants | Moderate Downgraded: imprecision, indirectness |
Total failure: day 42 (unadjusted) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ+AS) | RR 0.84 [0.54, 1.31] | 1 study · 1059 participants | Low Downgraded: imprecision, indirectness |
Serious adverse events (42 days) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ+AS) | RR 1 [0.25, 3.97] | 1 study · 1271 participants | Low Downgraded: imprecision, indirectness |
First treatment, ALT increase > 5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ+AS) | RR 7.48 [0.99, 56.45] | 1 study · 1271 participants | Low Downgraded: imprecision, indirectness |
First treatment, AST increase > 5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ+AS) | RR 9.49 [0.55, 162.64] | 1 study · 1271 participants | Very low Downgraded: imprecision, indirectness |
First treatment, bilirubin increase > 2.5 × ULN (42 days) Pyronaridine‐artesunate (PY‐AS) vs mefloquine plus artesunate (MQ+AS) | RR 3.49 [0.43, 28.29] | 1 study · 1271 participants | Very low Downgraded: imprecision, indirectness |
Pyronaridine‐artesunate (PY‐AS) compared to other antimalarials for adults and children with uncomplicated malaria
Population: adults and children with uncomplicated malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcomesa,b,c Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | no estimate extracted | NR | No studies |
Serious adverse events Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.24 [0.54, 2.84] | 7 studies · 3941 participants | Moderate Downgraded: imprecision |
First treatment, ALT increase > 5 × ULN Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 3.34 [1.63, 6.84] | 8 studies · 6614 participants | High |
First treatment, AST increase > 5 × ULN Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.8 [0.89, 3.65] | 8 studies · 6614 participants | Moderate Downgraded: imprecision, indirectness |
First treatment, bilirubin increase > 2.5 × ULN Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.03 [0.49, 2.18] | 7 studies · 6417 participants | Moderate Downgraded: imprecision |
Subsequent treatment(s), ALT > 5 × ULN Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 2.18 [0.76, 6.27] | 1 study · 1649 participants | Low Downgraded: imprecision, indirectness |
Subsequent treatment(s), AST > 5 × ULN Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.82 [0.74, 4.44] | 1 study · 1649 participants | Low Downgraded: imprecision, indirectness |
Subsequent treatment(s), bilirubin > 5 × ULN Pyronaridine‐artesunate (PY‐AS) vs other antimalarials | RR 1.13 [0.42, 3.01] | 1 study · 1649 participants | Low Downgraded: imprecision, indirectness |
Artesunate‐pyronaridine compared to artemether‐lumefantrine for uncomplicated falciparum malaria
Population: Adults and children with uncomplicated falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Treatment failure (day 28) Artesunate‐pyronaridine vs artemether‐lumefantrine | RR 0.6 [0.4, 0.9] | 2 studies · 1720 participants | Moderate Downgraded: risk of bias, imprecision, inconsistency, indirectness |
Treatment failure (Day 42) Artesunate‐pyronaridine vs artemether‐lumefantrine | RR 0.85 [0.53, 1.36] | 2 studies · 1691 participants | Moderate Downgraded: risk of bias, imprecision, inconsistency, indirectness |
Artesunate‐pyronaridine compared to artesunate plus mefloquine for treating uncomplicated P. falciparum malaria
Population: People with uncomplicatedP. falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Treatment failure (Day 28) Artesunate‐pyronaridine vs artesunate plus mefloquine | RR 0.35 [0.17, 0.73] | 1 study · 1200 participants | Moderate Downgraded: risk of bias, imprecision, inconsistency, indirectness |
Treatment failure (Day 42) Artesunate‐pyronaridine vs artesunate plus mefloquine | RR 0.86 [0.57, 1.31] | 1 study · 1146 participants | Moderate Downgraded: risk of bias, imprecision, inconsistency, indirectness |
Liver toxicity of pyronaridine compared to other antimalarials
Population: People with uncomplicated falciparum malaria
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Elevated alanine aminotransaminase levels Grade 3,4 toxicity Liver toxicity of pyronaridine vs other antimalarials | RR 4.17 [1.38, 12.61] | 4 studies · 3523 participants | Moderate Downgraded: risk of bias, imprecision, inconsistency, indirectness |
Elevated aspartate aminotransferase levels Grade 3, 4 toxicity Liver toxicity of pyronaridine vs other antimalarials | RR 4.08 [1.17, 14.26] | 4 studies · 3528 participants | Moderate Downgraded: risk of bias, imprecision, inconsistency, indirectness |
Elevated alkaline phosphatase levels Grade 3, 4 toxicity Liver toxicity of pyronaridine vs other antimalarials | RR 0.62 [0.15, 2.51] | 3 studies · 2606 participants | Moderate Downgraded: risk of bias, imprecision, inconsistency, indirectness |
Elevated bilirubin Grade 3, 4 toxicity Liver toxicity of pyronaridine vs other antimalarials | RR 1.92 [0.59, 6.24] | 3 studies · 3067 participants | Low Downgraded: risk of bias, imprecision, inconsistency, indirectness |