Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children : insights from randomized clinical trials and a real-world study
© 2024. The Author(s)..
BACKGROUND: Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine-artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM).
METHODS: An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to < 20 kg, who received at least one dose of study drug (paediatric safety population). PA was administered once daily for 3 days; two trials included the comparator artemether-lumefantrine (AL). PCR-adjusted day 28 adequate clinical and parasitological response (ACPR) was evaluated. Real-world PA granules safety and effectiveness was also considered.
RESULTS: In the integrated safety analysis, 63.9% (95% CI 60.2, 67.4; 426/667) of patients had adverse events following PA and 62.0% (95% CI 56.9, 66.9; 222/358) with AL. Vomiting was more common with PA (7.8% [95% CI 6.0, 10.1; 52/667]) than AL (3.4% [95% CI 1.9, 5.8; 12/358]), relative risk 2.3 (95% CI 1.3, 4.3; P = 0.004), occurring mainly following the first PA dose (6.7%, 45/667), without affecting re-dosing or adherence. Prolonged QT interval occurred less frequently with PA (3.1% [95% CI 2.1, 4.8; 21/667]) than AL (8.1% [95% CI 5.7, 11.4; 29/358]), relative risk 0.39 (95% CI 0.22, 0.67; P = 0.0007). In CANTAM, adverse events were reported for 17.7% (95% CI 16.3, 19.2; 460/2599) of patients, most commonly vomiting (5.4% [95% CI 4.6, 6.4; 141/2599]), mainly following the first dose, (4.5% [117/2599]), with all patients successfully re-dosed, and pyrexia (5.4% [95% CI 4.6, 6.3; 140/2599]). In the two comparative clinical trials, Day 28 ACPR in the per-protocol population for PA was 97.1% (95% CI 94.6, 98.6; 329/339) and 100% (95% CI 99.3, 100; 514/514) versus 98.8% (95% CI 95.7, 99.9; 165/167) and 98.4% (95% CI 95.5, 99.7; 188/191) for AL, respectively. In CANTAM, PA clinical effectiveness was 98.0% (95% CI 97.3, 98.5; 2273/2320).
CONCLUSIONS: Anti-malarial treatment with PA paediatric granules administered once daily for 3 days was well tolerated in children and displayed good clinical efficacy in clinical trials, with effectiveness confirmed in a real-world study. Trial registration Clinicaltrials.gov: SP-C-003-05: identifier NCT00331136; SP-C-007-07: identifier NCT0541385; SP-C-021-15: identifier NCT03201770. Pan African Clinical Trials Registry: SP-C-013-11: identifier PACTR201105000286876.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Malaria journal - 23(2024), 1 vom: 28. Feb., Seite 61 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ramharter, Michael [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.03.2024 Date Revised 02.03.2024 published: Electronic ClinicalTrials.gov: NCT00331136, NCT0541385, NCT03201770 Citation Status MEDLINE |
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| doi: |
10.1186/s12936-024-04885-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369089006 |
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| 100 | 1 | |a Ramharter, Michael |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children |b insights from randomized clinical trials and a real-world study |
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| 500 | |a Date Revised 02.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT00331136, NCT0541385, NCT03201770 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine-artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM) | ||
| 520 | |a METHODS: An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to < 20 kg, who received at least one dose of study drug (paediatric safety population). PA was administered once daily for 3 days; two trials included the comparator artemether-lumefantrine (AL). PCR-adjusted day 28 adequate clinical and parasitological response (ACPR) was evaluated. Real-world PA granules safety and effectiveness was also considered | ||
| 520 | |a RESULTS: In the integrated safety analysis, 63.9% (95% CI 60.2, 67.4; 426/667) of patients had adverse events following PA and 62.0% (95% CI 56.9, 66.9; 222/358) with AL. Vomiting was more common with PA (7.8% [95% CI 6.0, 10.1; 52/667]) than AL (3.4% [95% CI 1.9, 5.8; 12/358]), relative risk 2.3 (95% CI 1.3, 4.3; P = 0.004), occurring mainly following the first PA dose (6.7%, 45/667), without affecting re-dosing or adherence. Prolonged QT interval occurred less frequently with PA (3.1% [95% CI 2.1, 4.8; 21/667]) than AL (8.1% [95% CI 5.7, 11.4; 29/358]), relative risk 0.39 (95% CI 0.22, 0.67; P = 0.0007). In CANTAM, adverse events were reported for 17.7% (95% CI 16.3, 19.2; 460/2599) of patients, most commonly vomiting (5.4% [95% CI 4.6, 6.4; 141/2599]), mainly following the first dose, (4.5% [117/2599]), with all patients successfully re-dosed, and pyrexia (5.4% [95% CI 4.6, 6.3; 140/2599]). In the two comparative clinical trials, Day 28 ACPR in the per-protocol population for PA was 97.1% (95% CI 94.6, 98.6; 329/339) and 100% (95% CI 99.3, 100; 514/514) versus 98.8% (95% CI 95.7, 99.9; 165/167) and 98.4% (95% CI 95.5, 99.7; 188/191) for AL, respectively. In CANTAM, PA clinical effectiveness was 98.0% (95% CI 97.3, 98.5; 2273/2320) | ||
| 520 | |a CONCLUSIONS: Anti-malarial treatment with PA paediatric granules administered once daily for 3 days was well tolerated in children and displayed good clinical efficacy in clinical trials, with effectiveness confirmed in a real-world study. Trial registration Clinicaltrials.gov: SP-C-003-05: identifier NCT00331136; SP-C-007-07: identifier NCT0541385; SP-C-021-15: identifier NCT03201770. Pan African Clinical Trials Registry: SP-C-013-11: identifier PACTR201105000286876 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Plasmodium falciparum | |
| 650 | 4 | |a Anti-malarial | |
| 650 | 4 | |a Granule formulation | |
| 650 | 4 | |a Malaria | |
| 650 | 4 | |a Paediatric | |
| 650 | 4 | |a Pyronaridine–artesunate | |
| 650 | 7 | |a pyronaridine tetraphosphate, artesunate drug combination |2 NLM | |
| 650 | 7 | |a Antimalarials |2 NLM | |
| 650 | 7 | |a Artemether, Lumefantrine Drug Combination |2 NLM | |
| 650 | 7 | |a Artemisinins |2 NLM | |
| 650 | 7 | |a Artemether |2 NLM | |
| 650 | 7 | |a C7D6T3H22J |2 NLM | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
| 650 | 7 | |a Ethanolamines |2 NLM | |
| 650 | 7 | |a Artesunate |2 NLM | |
| 650 | 7 | |a 60W3249T9M |2 NLM | |
| 650 | 7 | |a Naphthyridines |2 NLM | |
| 700 | 1 | |a Djimde, Abdoulaye A |e verfasserin |4 aut | |
| 700 | 1 | |a Borghini-Fuhrer, Isabelle |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Jangsik |e verfasserin |4 aut | |
| 700 | 1 | |a Aspinall, Adam |e verfasserin |4 aut | |
| 700 | 1 | |a Richardson, Naomi |e verfasserin |4 aut | |
| 700 | 1 | |a Wibberg, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Fleckenstein, Lawrence |e verfasserin |4 aut | |
| 700 | 1 | |a Arbe-Barnes, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Duparc, Stephan |e verfasserin |4 aut | |
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