Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusions in Ugandan Children with Sickle Cell Anemia: Study Design of the Alternative Dosing And Prevention of Transfusions Trial.

Autor:	Power-Hays A; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA., Namazzi R; Global Health Uganda, Kampala, Uganda.; Makerere University, Kampala, Uganda., Kato C; Global Health Uganda, Kampala, Uganda., McElhinney KE; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Conroy AL; Global Health Uganda, Kampala, Uganda.; Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, Indiana, USA., Hume H; Division of Hematology/Oncology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Québec, Canada.; Department of Pediatrics, Université de Montréal, Montreal, Québec, Canada., John C; Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, Indiana, USA., O'Hara SM; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA., Stuber SE; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Lane A; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Latham TS; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Opoka RO; Aga Khan Medical College, Nairobi, Kenya., Ware RE; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Jazyk:	angličtina
Zdroj:	Acta haematologica [Acta Haematol] 2024 Jun 05, pp. 1-12. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1159/000539541
Abstrakt:	Introduction: People with sickle cell anemia (SCA) may require frequent blood transfusions to treat acute and chronic complications. Hydroxyurea is a life-saving treatment for SCA that could also decrease the need for blood transfusions. Inadequate medication access and challenges in dose optimization limit the widespread use of hydroxyurea in Africa. If feasible, pharmacokinetic (PK) dosing might improve dose determination to minimize toxicities and maximize clinical benefits. The Alternative Dosing And Prevention of Transfusions (ADAPT, NCT05662098) trial will analyze the impact of hydroxyurea on transfusion rate and serve as a pilot study to evaluate the feasibility of PK-guided hydroxyurea dosing in Uganda. Methods: Herein we describe the rationale and design of ADAPT, a prospective cohort study of ∼100 children with SCA in Jinja, Uganda. The primary hypothesis is that hydroxyurea will decrease blood transfusion use by ≥ 50%, comparing the transfusion incidence rate ratio between a 3-month pretreatment and a 12-month treatment period. A key secondary hypothesis is that our PK-dosing approach will generate a suitable hydroxyurea dose for ≥80% of participants. Every ADAPT participant will undergo hydroxyurea PK testing, and if a dose is generated within 15-35 mg/kg/day, participants will start on their individualized dose. If not, they will start on a default dose of 20 mg/kg/day. Hydroxyurea dose optimization will occur with periodic dose adjustments. Conclusion: Overall, demonstrating the reduction in blood transfusion utilization with hydroxyurea treatment would provide leverage to increase hydroxyurea access, and PK-guided hydroxyurea dosing should optimize the safe and effective treatment of SCA across sub-Saharan Africa. (© 2024 S. Karger AG, Basel.)
Databáze:	MEDLINE
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