Hydroxyurea Effective for Stroke Prevention in Children with Sickle Cell Disease in Tanzania

Sickle cell disease (SCD) is prevalent (1.5% of live births) in sub-Saharan countries, yet limited research has been done in this region due to lack a basic clinical care. Stroke, either silent or overt, is a major cause of morbidity and mortality in children with SCD and transcranial Doppler (TCD) screening is a standard of care to identify those at risk.

In a prospective, open-label, phase 2 trial researchers addressed whether treatment with hydroxyurea at maximal tolerated dose (MTD) can reduce the risk of stroke in children with SCD in Tanzania. The investigators also focused on building infrastructure to perform TCD for stroke screening at local institutions.

The study enrolled 196 children with SCD aged 2 to 16 years. All participants underwent TCD screening at enrollment. The TCD interpretations were as follows: 22% conditional (170–199 cm/sec), 2% abnormal (≥200 cm/sec), and 75% normal; 1% had inadequate exams. Among the 47 patients with elevated TCD velocity, 45 were treated with hydroxyurea (starting at 20 mg/kg daily) escalated per protocol to the MTD. At 12 months the mean dose was 27.4 mg/kg daily; this dose was maintained with slight adjustments for another 12 months. Treatment response was analyzed after 12 and 24 months.

No overt strokes occurred during the trial (silent stroke detection was not possible due to lack of access to brain MRI). Of 42 participants who had a TCD examination after 12 months of hydroxyurea treatment, 83% had reversion to normal velocities. No serious treatment-related adverse events occurred. Among 142 patients with normal TCD velocities at baseline, 6% had elevated TCD velocity at 12 months and were started on hydroxyurea.