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.