Abstract:
Despite its well-described safety and efficacy in the treatment of sickle cell anemia
(SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan
Africa, where more than 75% of annual SCA births occur and many comorbidities exist.
Realizing Effectiveness Across Continents with Hydroxyurea (REACH,
ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of
hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea
treatment for children with SCA in four sub-Saharan African countries. Following
comprehensive training of local research teams, REACH was approved by local Ethics
Committees and achieved full enrollment ahead of projections with 635 participants
enrolled over a 30-month period, despite half of families living >12 km from their
clinical site. At enrollment, study participants (age 5.4 ± 2.4 years) had substantial
morbidity, including a history of vaso-occlusive pain (98%), transfusion (68%), malaria
(85%), and stroke (6%). Significant differences in laboratory characteristics were noted
across sites, with lower hemoglobin concentrations (P < .01) in Angola (7.2 ± 1.0 g/dL)
and the DRC (7.0 ± 0.9 g/dL) compared to Kenya (7.4 ± 1.1 g/dL) and Uganda (7.5 ± 1.1
g/dL). Analysis of known genetic modifiers of SCA demonstrated a high frequency of αthalassemia (58.4% with at least a single α-globin gene deletion) and G6PD deficiency
(19.7% of males and 2.4% of females) across sites. The CAR β-globin haplotype was
present in 99% of participants. The full enrollment to REACH confirms the feasibility of
conducting high-quality SCA research in Africa; this study will provide vital information
to guide safe and effective dosing of hydroxyurea for children with SCA living in Africa.