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
Abstract 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 p...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-024-04885-3 |
| _version_ | 1797275779046834176 |
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| author | Michael Ramharter Abdoulaye A. Djimde Isabelle Borghini-Fuhrer Robert Miller Jangsik Shin Adam Aspinall Naomi Richardson Martina Wibberg Lawrence Fleckenstein Sarah Arbe-Barnes Stephan Duparc |
| author_facet | Michael Ramharter Abdoulaye A. Djimde Isabelle Borghini-Fuhrer Robert Miller Jangsik Shin Adam Aspinall Naomi Richardson Martina Wibberg Lawrence Fleckenstein Sarah Arbe-Barnes Stephan Duparc |
| author_sort | Michael Ramharter |
| collection | DOAJ |
| description | Abstract 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 |
| first_indexed | 2024-03-07T15:19:21Z |
| format | Article |
| id | doaj.art-c0a0c67d6b674912b88c1f867080b596 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-03-07T15:19:21Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-c0a0c67d6b674912b88c1f867080b5962024-03-05T17:45:01ZengBMCMalaria Journal1475-28752024-02-0123111810.1186/s12936-024-04885-3Safety and efficacy of pyronaridine–artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world studyMichael Ramharter0Abdoulaye A. Djimde1Isabelle Borghini-Fuhrer2Robert Miller3Jangsik Shin4Adam Aspinall5Naomi Richardson6Martina Wibberg7Lawrence Fleckenstein8Sarah Arbe-Barnes9Stephan Duparc10Department of Tropical Medicine, Bernhard Nocht Institute for Tropical MedicineMalaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB)Medicines for Malaria VentureArtemida PharmaShin Poong Pharm. Co. LtdMedicines for Malaria VentureMagenta Communications LtdDATAMAP GmbHDepartment of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of IowaArtemida PharmaMedicines for Malaria VentureAbstract 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 PACTR201105000286876https://doi.org/10.1186/s12936-024-04885-3MalariaPlasmodium falciparumPyronaridine–artesunatePaediatricAnti-malarialGranule formulation |
| spellingShingle | Michael Ramharter Abdoulaye A. Djimde Isabelle Borghini-Fuhrer Robert Miller Jangsik Shin Adam Aspinall Naomi Richardson Martina Wibberg Lawrence Fleckenstein Sarah Arbe-Barnes Stephan Duparc 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 Malaria Journal Malaria Plasmodium falciparum Pyronaridine–artesunate Paediatric Anti-malarial Granule formulation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Malaria Plasmodium falciparum Pyronaridine–artesunate Paediatric Anti-malarial Granule formulation |
| url | https://doi.org/10.1186/s12936-024-04885-3 |
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