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However, the most efficacious and safest dose is unknown, particularly in children. This trial assessed the safety, tolerability, and efficacy of two high-dose PQ regimens compared with standard of care (SoC) in children with\n                      <jats:italic>P. vivax<\/jats:italic>\n                      infections in the Brazilian Amazon.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CHILDPRIM was an open-label, randomized clinical trial conducted in Manaus and Cruzeiro do Sul, Brazilian Amazon, from August 2021 to January 2025. The study evaluated the non-inferiority of high-dose PQ regimens in terms of safety, tolerability, and parasitological response at day 180 compared to the low-dose regimen in children under 15\u00a0years of age with uncomplicated\n                      <jats:italic>P. vivax<\/jats:italic>\n                      malaria. Participants were randomized (1:1:1) to receive: (1) Brazilian routine standard-dose PQ (3.5\u00a0mg\/kg over 7\u00a0days)\u20130.5\u00a0mg\/kg\/day; (2) high-dose PQ long-course (7.0\u00a0mg\/kg over 14\u00a0days)\u20130.5\u00a0mg\/kg\/day; or (3) high-dose PQ short-course (7.0\u00a0mg\/kg over 7\u00a0days)\u20131.0\u00a0mg\/kg\/day, after glucose-6-phosphate dehydrogenase (G6PD) deficiency screening using the quantitative SD Biosensor. All participants were followed for 180\u00a0days. The primary outcomes were the proportion of participants experiencing adverse events of any intensity and the proportion of failures up to day 180 between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 100 individuals were randomized: 32 in the PQ 3.5\u00a0mg\/kg over 7d arm, 34 in the PQ 7.0\u00a0mg\/kg over 14d arm, and 34 in the PQ 7.0\u00a0mg\/kg over 7d arm. The most common adverse events were methaemoglobinaemia, anaemia, and gastrointestinal symptoms. Higher doses of PQ resulted in more adverse events, but no more serious adverse events. Participants in the PQ 3.5\u00a0mg\/kg over 7d arm presented a higher risk of recurrence at 42 and 180\u00a0days, which is why the trial was halted after the second interim analysis. Kaplan\u2013Meier estimates of the percentage of participants who were free from recurrence at day 180 were 50% in PQ 3.5\u00a0mg\/kg over 7d arm (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200916), 82.3% in PQ 7.0\u00a0mg\/kg over 14d arm (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200928), and 79.4% in PQ 7.0\u00a0mg\/kg over 7d arm (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200927) (log-rank;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0065).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      High-dose PQ regimens (7.0\u00a0mg\/kg total) were safe, well tolerated, and significantly reduced\n                      <jats:italic>P. vivax<\/jats:italic>\n                      recurrence in children without G6PD deficiency. Both 7- and 14-day schedules showed comparable efficacy, with rare SAEs and normalization of Hb and methaemoglobinaemia by day 28. Given their similar efficacy, the shorter regimen may offer advantages for adherence and programmatic implementation in endemic settings.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      ClinicalTrials.gov, TRN: NCT05044637, Registration Date: 20 August 2021.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-025-05686-y","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T21:06:01Z","timestamp":1766437561000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety, tolerability, and efficacy of high versus low-dose, short versus long-course daily primaquine for the radical cure of uncomplicated Plasmodium vivax malaria in children under 15\u00a0years of age: an open-label, non-inferiority, randomized controlled trial (CHILDPRIM)"],"prefix":"10.1186","volume":"25","clinical-trial-number":[{"clinical-trial-number":"nct05044637","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ana Luisa O.","family":"Pacheco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aretha G.","family":"Omena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djane C.","family":"Ba\u00eda-da-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyane A. 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