Hydroxyurea to lower transcranial doppler velocities and prevent primary stroke: the Uganda NOHARM sickle cell anemia cohort

Robert Opoka, Aga Khan University
Heather Hume, Makerere University, Uganda
Teresa Latham, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA
Adam Lane, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA
Olatundun Williams, Lurie Children’s Hospital of Chicago, USA
Jennifer Tymon, St. Luke’s University Health Network, Panama
Maria Nakafeero, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA
Phillip Kasirye, Makerere University, Uganda
Christopher Ndugwa, Makerere University, Uganda
Chandy John, University of Indiana, Indiana

This work was published before the author joined Aga Khan University.

Abstract

In sub-Saharan Africa, sickle cell anemia (SCA) remains a significant public health problem with high mortality: an estimated 50-90% of affected children die before 5 years of age.1 A high prevalence of stroke is particularly devastating for children and has substantial morbidity.2,3 Hydroxyurea is now recommended across the lifespan as a safe and effective disease-modifying therapy for SCA,4,5 but is not routinely available in sub-Saharan Africa.6

NOHARM (NCT01976416), a randomized double-blinded, placebo-controlled trial, was among the first prospective studies to investigate hydroxyurea treatment for children with SCA living in a malaria endemic region within Africa. The NOHARM trial consisted of a blinded phase (Year 1) and an open-label phase (Year 2).7 Initially children 1.00-4.99 years of age were randomized either to placebo or fixed-dose hydroxyurea (20 mg/kg/day). The Year 1 results demonstrated that short-term hydroxyurea treatment was both safe and efficacious in this young patient population living in a malarial endemic region. [8] We now analyze Year 2 data from the open-label phase, in which all NOHARM participants received hydroxyurea at 20 mg/kg/day, to compare the effects of hydroxyurea on SCA-related morbidity and also to provide serial transcranial Doppler (TCD) data, which were not included in the original randomized report.