Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia
نویسنده :
تاریخ انتشار : 1397/02/18
Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living
in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic
sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro
studies suggest hydroxyurea could increase malaria severity, and hydroxyureaassociated
neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea
in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled
trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at
20 6 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinicalmalaria.
Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory
effects, and hematological toxicities. Children received either hydroxyurea (N 5 104) or
placebo (N 5 103). Malaria incidence did not differ between children on hydroxyurea (0.05
episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07
episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate
ratio was 0.7 ([0.2, 2.7]; P 5 .61). Time to infection also did not differ significantly between
treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis,
dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo
(69%; P 5 .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with
decreasedleukocytes and reticulocytes.Serious AEs, sepsis episodes, and dose-limiting toxicitieswere similar between treatment arms.
Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA
living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related
laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at
www.clinicaltrials.gov as #NCT01976416