{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T09:54:59Z","timestamp":1765619699744,"version":"3.37.3"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004167","name":"Medicines for Malaria Venture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004167","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine\u2013artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed <jats:italic>Plasmodium falciparum<\/jats:italic>, body weight\u2009\u2265\u20095\u00a0kg to &lt;\u200920\u00a0kg, who received at least one dose of study drug (paediatric safety population). PA was administered once daily for 3\u00a0days; two trials included the comparator artemether\u2013lumefantrine (AL). PCR-adjusted day 28 adequate clinical and parasitological response (ACPR) was evaluated. Real-world PA granules safety and effectiveness was also considered.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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; <jats:italic>P<\/jats:italic>\u2009=\u20090.004), 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; <jats:italic>P<\/jats:italic>\u2009=\u20090.0007). 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).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Anti-malarial treatment with PA paediatric granules administered once daily for 3\u00a0days was well tolerated in children and displayed good clinical efficacy in clinical trials, with effectiveness confirmed in a real-world study.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> 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<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-024-04885-3","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T17:04:46Z","timestamp":1709139886000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and efficacy of pyronaridine\u2013artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study"],"prefix":"10.1186","volume":"23","clinical-trial-number":[{"clinical-trial-number":"nct00331136","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct0541385","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03201770","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"pactr201105000286876","registry":"10.18810\/pactr"}],"author":[{"given":"Michael","family":"Ramharter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdoulaye A.","family":"Djimde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Borghini-Fuhrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jangsik","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Aspinall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Wibberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Fleckenstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Arbe-Barnes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Duparc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"4885_CR1","unstructured":"WHO. 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Cochrane Database Syst Rev. 2019;1:CD006404.","journal-title":"Cochrane Database Syst Rev"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-024-04885-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12936-024-04885-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-024-04885-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T17:05:48Z","timestamp":1709139948000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-024-04885-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,28]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4885"],"URL":"https:\/\/doi.org\/10.1186\/s12936-024-04885-3","relation":{},"ISSN":["1475-2875"],"issn-type":[{"type":"electronic","value":"1475-2875"}],"subject":[],"published":{"date-parts":[[2024,2,28]]},"assertion":[{"value":"29 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients, or their parents\/guardians, provided written informed consent, and children able to understand the study gave signed assent. Ethics approval for the individual studies was granted as follows. SP-C-003-05: Gabon, Ethics Committee of the International Foundation for the Albert Schweitzer Hospital in Lambar\u00e9n\u00e9. SP-C-007-07: Burkina Faso, Comit\u00e9 national d\u2019\u00e9thique, Minist\u00e8re de la Sant\u00e9\u2014Minist\u00e8re des enseignements secondaires sup\u00e9rieurs et de la recherche scientifique\u2014Comit\u00e9 d\u2019Ethique pour la recherche en Sant\u00e9; Democratic Republic of Congo, Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et Universitaire, Ecole de sant\u00e9 Publique, Comit\u00e9 d\u2019Ethique Universit\u00e9 de Kinshasa, facult\u00e9 de M\u00e9decine; C\u00f4te d\u2019Ivoire, Minist\u00e8re de la Sant\u00e9 et de l\u2019Hygi\u00e8ne Publique\u2014Comit\u00e9 National d\u2019Ethique des Sciences de la Vie et de la Sant\u00e9 (CNESVS); Kenya, Kenyatta National Hospital Ethic Committee; Mali, Minist\u00e8re de l\u2019Education Nationale, Comit\u00e9 Institutionnel d\u2019Ethique de la Facult\u00e9 de M\u00e9dicine de Pharmacie et d\u2019Odonto Stomatologie Universit\u00e9 de Bamako; The Philippines, Research Institute for Tropical Medicine Institutional\/Ethical Review Board; Gabon, Comit\u00e9 d\u2019Ethique R\u00e9gional Ind\u00e9pendant de Lambar\u00e9n\u00e9 (CERIL). SP-C-013-11: Mali, Facult\u00e9 de M\u00e9dicine de Pharmacie et d'Odonto Stomatologie; Burkina Faso, Minist\u00e8re de la Sant\u00e9\/Minist\u00e8re de la Recherche Scientifique et de l\u2019Innovation; Guinea, Comit\u00e9 National d\u2019Ethique pour la Recherche en Sant\u00e9. SP-C-021-15: Cameroon, Comit\u00e9 National d\u2019Ethique de la Recherche pour la Sant\u00e9 Humaine; Democratic Republic of Congo, Comit\u00e9 d\u2019Ethique de l\u2019Universit\u00e9 Protestante au Congo; Gabon, Comit\u00e9 Nationale d\u2019Ethique et de la Recherche Scientifique and Comit\u00e9 d\u2019Ethique Institutionnel Albert Schweitzer Hospital, Lambar\u00e9n\u00e9; C\u00f4te d\u2019Ivoire, Comit\u00e9 Nationale d\u2019Ethique et de la Recherche Scientifique and Comit\u00e9 National d\u2019Ethique des Sciences de la Vie et de Sant\u00e9; and Republic of Congo, Comit\u00e9 d'\u00e9thique institutionnel de la Fondation Congolaise pour la Recherche M\u00e9dicale.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Stephan Duparc, Isabelle Borghini-Fuhrer and Adam Aspinall are employees of Medicines for Malaria Venture. Sarah Arbe-Barnes and Robert Miller are employees of Artemida Pharma. Jangsik Shin is an employee of Shin Poong Pharm. Co. Ltd. Naomi Richardson is an employee of Magenta Communications Ltd. which received funds from Medicines for Malaria Venture associated with this study. Martina Wibberg is an employee of DATAMAP GmbH which received funds from Medicines for Malaria Venture associated with this study. Michael Ramharter, Abdoulaye Djimde and Lawrence Fleckenstein declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"61"}}