Stroke Avoidance for Children in REpública Dominicana (SACRED): Protocol for a Prospective Study of Stroke Risk and Hydroxyurea Treatment in Sickle Cell Anemia

• Published in: JMIR research protocols 2017-06, Vol.6 (6), p.e107-e107
• Main Authors: Jeste, Neelum D, Sánchez, Luisanna M, Urcuyo, Gabriela S, Bergés, Melissa E, Luden, Judy P, Stuber, Susan E, Latham, Teresa S, Mena, Rafael, Nieves, Rosa M, Ware, Russell E
• Format: Article
• Language: English
• Subjects: Age; Blood; Blood transfusions; Clinical medicine; Disease prevention; Hemoglobin; Laboratories; Mortality; Patients; Pediatrics; Protocol; Sickle cell anemia; Stroke; Veins & arteries; Velocity
• ISSN: 1929-0748; 1929-0748
• DOI: 10.2196/resprot.7491

In the Dominican Republic, where the burden of sickle cell anemia (SCA) is high, many children lack access to routine screening and preventative care. Children with SCA are at risk for stroke, an event that leads to significant morbidity and mortality. In the United States, screening via transcranial Doppler (TCD) identifies children with SCA at highest stroke risk, allowing early intervention with blood transfusions. The need for indefinite transfusions for primary stroke prevention limits their practicality in limited-resource countries. Hydroxyurea has been shown to lower TCD velocities and to prevent conversion from conditional (170 to 199 cm/sec) to abnormal (greater than or equal to 200 cm/sec) velocities. In resource-limited settings, implementation of a TCD screening program, coupled with hydroxyurea therapy, could reduce the burden of SCA and stroke. The aims of the Stroke Avoidance for Children in REpública Dominicana (SACRED) trial are (1) to screen children with SCA for stroke risk using TCD and to determine the prevalence of elevated velocities in a cross-sectional sample; (2) to identify clinical and laboratory correlates of elevated velocities; and (3) to obtain longitudinal data on the natural history of TCD velocities and to measure therapeutic effects of hydroxyurea. This prospective trial, designed and conducted by Cincinnati Children's Hospital Medical Center (CCHMC) and Hospital Infantil Robert Reid Cabral (HIRRC) with Centro de Obstetricia y Ginecología, includes a baseline cross-sectional epidemiological survey of the distribution of TCD velocities across a large cohort of children with SCA in the Dominican Republic. Children with conditional velocities are eligible to begin protocol-directed hydroxyurea if laboratory criteria are met. The treatment schedule begins with a fixed-dose of approximately 20 mg/kg/day for 6 months, after which it escalates to maximum tolerated dose (MTD). All participants undergo longitudinal annual TCD evaluation, while those on hydroxyurea have semi-annual evaluations during the 3-year study period. Data are collected using an Internet-based Research Electronic Data Capture (REDCap) system with forms translated into Spanish; both remote and on-site monitoring are used. To date, 122 children with SCA have enrolled in SACRED including 85 (69.7%, 85/122) with normal, 29 (23.8%, 29/122) with conditional, 5 (4.1%, 5/122) with abnormal, and 3 (2.5%, 3/122) with inadequate TCD velocities. Of the 29 children wit