Hydroxyurea - Pragmatic Reduction in Mortality and Economic burden (H-PRIME): A 2x2x2 factorial randomized open-label trial investigating practical approaches to the treatment of sickle cell disease at four sites in Eastern Uganda.

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dc.contributor.authorOlupot-Olupot, Peter
dc.contributor.authorAmorut, Denis
dc.contributor.authorOngodia, Paul
dc.contributor.authorOkalebo, B. Charles
dc.contributor.authorAbeso, Julian
dc.contributor.authorAloroker, Florence
dc.contributor.authorAsio, Sarah
dc.contributor.authorOdiit, Amos
dc.contributor.authorKiyaga, Charles
dc.contributor.authorMuhindo, Rita
dc.contributor.authorUyoga, Sophie
dc.contributor.authorMochamah, George
dc.contributor.authorMuyinda, Asad
dc.contributor.authorAbongo, Grace
dc.contributor.authorNyutu, Gideon
dc.contributor.authorMogaka, Christabel
dc.contributor.authorMaitland, Kathryn
dc.contributor.authorWalker, Sarah Ann
dc.contributor.authorGibb, Diana
dc.contributor.authorConnon, Roisin
dc.contributor.authorGeorge, Elizabeth
dc.contributor.authorWare, E Russell
dc.contributor.authorWilliams, N. Thomas
dc.date.accessioned2026-07-01T14:21:20Z
dc.date.available2026-07-01T14:21:20Z
dc.date.issued2025
dc.descriptionArticle
dc.description.abstractBackground Sickle cell disease is the most common and severe genetic disease in humans worldwide. The majority of those affected are born in subSaharan Africa, where resources to diagnose and manage them are often limited. Fresh approaches to the pragmatic management of children with sickle cell disease in Africa that improve both morbidity and mortality are urgently needed. Methods Hydroxyurea - Pragmatic Reduction in Mortality and Economic burden (H-PRIME) is a 2 × 2 × 2 factorial randomized open-label trial that is investigating three separate interventions. Eighteen hundred children aged 1-10 years attending sickle cell clinics at one of four sites in Eastern Uganda are being randomized to: (1) hydroxyurea administered at a low dose (10 mg/kg/day) versus high dose (25mg/kg/day), prescribed pragmatically through a weight-band-based approach and with clinically, rather than laboratory-guided monitoring; (2) enhanced malaria prophylaxis with weekly doses of dihydroartemisinin-piperaquine versus monthly doses of sulfadoxinepyrimethamine (standard of care); and (3) enhanced antibacterial prophylaxis with daily cotrimoxazole throughout life versus twice daily penicillin until the age of 5 years (standard of care). All children will be followed up for 48 months after the date on which the first child was randomized. The primary endpoint for the hydroxyurea randomization will be mortality, for the antimalarial random will be malaria-associated hospital admission, and for the antimicrobial randomization will be all-cause hospital admission. Secondary outcomes will include the incidence of sickle-specific complications, receipt of blood transfusions, hemoglobin and fetal hemoglobin concentrations, and economic costs and benefits of the three interventions. Conclusions The first participant was recruited for the trial on January 16, 2024. In total, 1487 of the 1800 target children were recruited by February 17, 2025. H-PRIME will efficiently answer three important pragmatic questions regarding the management of children with sickle cell disease in Africa. Keywords sickle cell disease, hydroxyurea, malaria, bacterial infections, Uganda
dc.description.sponsorshipThe Department of Health and Social Care (DHSC) ; Foreign, Commonwealth ; Development Office (FCDO), the Medical Research Council (MRC) ; Busitema University.
dc.identifier.citationOlupot-Olupot P, Amorut D, Ongodia P et al. Hydroxyurea - Pragmatic Reduction in Mortality and Economic burden (H-PRIME): A 2x2x2 factorial randomised open-label trial investigating practical approaches to the treatment of sickle cell disease at four sites in Eastern Uganda [version 1; peer review: 1 approved, 1 approved with reservations] Wellcome Open Research 2025, 10:244 https://doi.org/10.12688/wellcomeopenres.24096.1
dc.identifier.urihttps://bdears.busitema.ac.ug/handle/123456789/7086
dc.language.isoen
dc.publisherWellcome Open Research
dc.titleHydroxyurea - Pragmatic Reduction in Mortality and Economic burden (H-PRIME): A 2x2x2 factorial randomized open-label trial investigating practical approaches to the treatment of sickle cell disease at four sites in Eastern Uganda.
dc.typeArticle
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