Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial

• Published in: Blood Vol. 141; no. 8; pp. 825 - 834
• Main Authors: Abdullahi, Shehu U., Sunusi, Surayya, Abba, Mohammed Sani, Sani, Saifuddeen, Inuwa, Hauwau Aminu, Gambo, Safiya, Gambo, Awwal, Musa, Bilya, Covert Greene, Brittany V., Kassim, Adetola A., Rodeghier, Mark, Hussaini, Nafiu, Ciobanu, Mariana, Aliyu, Muktar H., Jordan, Lori C., DeBaun, Michael R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.02.2023; The American Society of Hematology
• Subjects: Anemia, Sickle Cell - complications; Antisickling Agents - therapeutic use; Child; Clinical Trials and Observations; Humans; Hydroxyurea - therapeutic use; Nigeria; Secondary Prevention - methods; Stroke - etiology; Nigeria
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2022016620

•Both low and moderate doses of hydroxyurea are efficacious for secondary stroke prevention in low-resource settings.•The median time between the initial stroke and death was less than a year, 0.8 years (interquartile range, 0.2-0.9). [Display omitted] We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval [CI], 0.32-3.00; P = .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18; 95% CI, 0.30-4.88; P = .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention. The risk of recurrent stroke in untreated sickle cell anemia (SCA) is high, necessitating chronic transfusion therapy where resources allow. To identify feasible alternative therapy for children with SCA in resource-limited areas, Abdullahi and colleagues undertook a randomized, double-blind trial of 2 fixed-dose regimens of hydroxyurea. In this Plenary Paper, the authors provide evidence that both low- and moderate-dose hydroxyurea regimens are effective for secondary stroke prevention when chronic transfusion therapy is not possible.