Children with
sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop
stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of
hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher
stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative
therapy (
hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ(0) -
thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0-35%) in the
hydroxyurea arm and 47% (95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on
hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with
hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No
stroke events occurred in either arm.
Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities.