Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III...

Area of Science:

• Pediatric Neurology
• Hematology
• Medical Imaging

Background:

• Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) face an increased risk of stroke.
• Current standard care for conditional TCD velocities is observation due to limited clinical data on preventative therapies.
• The efficacy of hydroxyurea in preventing conversion to abnormal TCD velocities (≥200 cm/sec) has not been prospectively evaluated in a randomized trial.

Purpose of the Study:

• To compare the efficacy of hydroxyurea versus standard observation in preventing conversion from conditional to abnormal TCD velocities in children with SCA.
• To assess the effect of hydroxyurea on TCD velocities in pediatric SCA patients.

Main Methods:

• The Sparing Conversion to Abnormal TCD Elevation (SCATE) trial was a Phase III multicenter international clinical trial.
• 38 children with SCA and conditional TCD velocities were enrolled and randomized to receive either hydroxyurea or observation.
• The trial was terminated early due to slow patient accrual; intention-to-treat and post hoc analyses were performed.

Main Results:

• In intention-to-treat analysis, the cumulative incidence of abnormal TCD conversion was 9% with hydroxyurea versus 47% with observation at 15 months (P=0.16).
• Post hoc analysis showed significantly fewer children on hydroxyurea converted to abnormal TCD velocities compared to observation (0% vs. 50%, P=0.02).
• Hydroxyurea treatment led to a significant reduction in mean TCD velocity (-15.5 cm/sec) compared to observation (+10.2 cm/sec) (P=0.02), with no stroke events in either group.

Conclusions:

• Hydroxyurea significantly reduces TCD velocities in children with SCA and conditional velocities, suggesting a potential benefit in preventing stroke conversion.
• Although the trial was terminated early, results indicate hydroxyurea may be more effective than observation in preventing the progression to abnormal TCD velocities.
• Further research is warranted to confirm these findings and establish hydroxyurea as a standard preventative therapy for this high-risk pediatric SCA population.