Hydroxyurea Therapy for Children With Sickle Cell Anemia in Sub-Saharan Africa: Rationale and Design of the REACH Trial.

BACKGROUND: Sickle cell anemia (SCA) is an inherited hematological disorder that causes a large but neglected global health burden, particularly in Africa. Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries. In sub-Saharan Africa, there is minimal use of hydroxyurea, due to lack of data, absence of evidence-based guidelines, and inexperience among healthcare providers. PROCEDURE: A partnership was established between investigators in North America and sub-Saharan Africa, to develop a prospective multicenter research protocol designed to provide data on the safety, feasibility, and benefits of hydroxyurea for children with SCA. RESULTS: The Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) trial is a prospective, phase I/II open-label dose escalation study of hydroxyurea that will treat a total of 600 children age 1-10 years with SCA: 150 at each of four different clinical sites within sub-Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda). The primary study endpoint will be severe hematological toxicities that occur during the fixed-dose treatment phase. REACH has an adaptive statistical design that allows for careful assessment of toxicities to accurately identify a safe hydroxyurea dose. CONCLUSIONS: REACH will provide data that address critical gaps in knowledge for the treatment of SCA in sub-Saharan Africa. By developing local expertise with the use of hydroxyurea and helping to establish treatment guidelines, the REACH trial results will have the potential to transform care for children with SCA in Africa.