NCT03948867

Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE)

Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE): A Prospective Trial to Reduce Primary Stroke in Children With Sickle Cell Anaemia

• Status: Enrolling By Invitation
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 202 (estimated)
• Sponsor: Children's Hospital Medical Center, Cincinnati · Academic / Other
• Sex: All
• Age: 2 Years – 16 Years
• Healthy volunteers: Not accepted

Summary

This study will 1) Evaluate the prevalence of elevated (conditional or abnormal) transcranial Doppler (TCD) velocities in a cross-sectional analysis of children with Sickle Cell Anemia (SCA) living in Tanzania; 2) Obtain longitudinal data on TCD velocities in this population; and 3) Measure the effects of hydroxyurea therapy on TCD velocities and associated primary stroke risk.

Detailed description

Stroke Prevention with Hydroxyurea Enabled through Research and Education (SPHERE) is a single-center prospective phase 2 pilot study. It will enroll a convenience sample of children with SCA, obtain cross-sectional baseline data at enrolment, and follow them as a prospective cohort for a period of 24 months. The cohort will be divided into two arms based on the initial screening TCD result: 1) those who have a normal (less than 170 cm/sec time averaged mean velocity (TAMV)) initial screening TCD and will be an observation/control cohort; and 2) those who have an elevated initial screening TCD (either conditional (170-199 cm/sec) or abnormal (greater than or equal to 200 cm/sec) TAMV) and will be a treatment cohort that receives open-label hydroxyurea therapy as per the dosing and administration schedule. Those who are found to have a normal TCD at enrolment and are part of the observation/control cohort will undergo repeat TCD 12 months after enrolment. If the TCD at 12 months has changed to an elevated velocity (conditional or abnormal), the study participant can begin study treatment, but will not be included in the primary endpoint analysis. The primary hypothesis is after 12 months of hydroxyurea therapy, children with conditional TCD velocities will achieve a mean decrease of \>15cm/sec from their baseline TCD TAMV.

Conditions

• Sickle Cell Anemia in Children

Interventions

Type	Name	Description
DRUG	Hydroxyurea	Hydroxyurea treatment will be provided to reduce stroke risk. Hydroxyurea treatment will be started at a fixed dose of 20.0 ± 5.0 mg/kg/day, followed by escalation to maximum tolerated dose (MTD).
DIAGNOSTIC_TEST	Elevated Arm TCD Examination	TCD examination on children with SCA between ages 2 and 16 years of age will be completed to evaluate their risk of stroke. For children with elevated velocities at initial screening or at 1 Year who receive hydroxyurea therapy, TCD examinations will occur every 6 ± 2 months.
DIAGNOSTIC_TEST	Normal Arm TCD Examination	TCD examination on children with SCA between ages 2 and 16 years of age will be completed to evaluate their risk of stroke. TCD examination for all participants will occur at initial screening, at Year 1 (12 ± 3 months), and Year 2 (24 ± 3 months). Children with normal TCD velocities at initial screening will undergo repeat TCD 12 months after enrolment. If the TCD at 12 months has changed to an elevated velocity (conditional or abnormal), the child can begin study treatment (Hydroxyurea).

Timeline

• Start date: 2019-04-24
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2019-05-14
• Last updated: 2025-07-17

Locations

2 sites across 2 countries: United States, Tanzania

Regulatory

• FDA-regulated drug study