Realizing effectiveness across continents with hydroxyurea: Enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa
McGann PT, Williams TN, Olupot-Olupot P, Tomlinson GA, Lane A, Luis Reis da Fonseca J, Kitenge R, Mochamah G, Wabwire H, Stuber S, Howard TA, McElhinney K, Aygun B, Latham T, Santos B, Tshilolo L, Ware RE, REACH Investigators
Am J Hematol. 2018;93
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 alpha-thalassemia (58.4% with at least a single alpha-globin gene deletion) and G6PD deficiency (19.7% of males and 2.4% of females) across sites. The CAR beta-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.