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

NCT ID: NCT03948867

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-24
• Study Completion Date: 2026-12-31

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Elevated Initial Screening TCD

Those who have an elevated initial screening TCD (either conditional or abnormal TAMV) and will be a treatment cohort that receives open-label hydroxyurea therapy as per the dosing and administration schedule.

Group Type: EXPERIMENTAL

Hydroxyurea

Intervention Type: DRUG

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).

Elevated Arm TCD Examination

Intervention Type: DIAGNOSTIC_TEST

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.

Normal Initial Screening TCD

Those who are found to have a normal TCD at enrolment are a part of the observation/control cohort and will undergo repeat TCD every 12 months after enrolment. If the TCD at 12 months has changed to an elevated velocity (conditional or abnormal), the study participant will be reassigned to the elevated initial screening TCD arm and can begin study treatment (hydroxyurea), but will not be included in the primary endpoint analysis.

Group Type: EXPERIMENTAL

Normal Arm TCD Examination

Intervention Type: DIAGNOSTIC_TEST

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).

Interventions

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).

Intervention Type: DRUG

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.

Intervention Type: 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).

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Willingness to sign informed consent
• Willingness to follow all study procedures
• Available for study visits for the duration of the study and no plans to move away from study center.
• Confirmed diagnosis of Sickle Cell Anemia (SCA) by haemoglobin electrophoresis.
• Able to take oral medication and follow hydroxyurea treatment schedule.

Exclusion Criteria

• Febrile illness within the past two weeks. (Temporary Exclusion)
• Hospitalized within the past two weeks. (Temporary Exclusion)
• Transfusion within the past two weeks. (Temporary Exclusion)

Patients who enroll in the screening portion, have a conditional or abnormal TCD, and are eligible to start hydroxyurea will be excluded from receiving study treatment if they meet any of the following criteria:

• Abnormal pre-enrolment laboratory values (Temporary Exclusion)
• Known medical condition making participation ill-advised.
• Known allergic reactions to components of hydroxyurea.
• Previous history of stroke.
• Currently pregnant or lactating.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bugando Medical Centre

UNKNOWN

Sponsor Role: collaborator

The American Society of Hematology

UNKNOWN

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Bugando Medical Centre

Mwanza, , Tanzania

Countries

United States; Tanzania

References

Ambrose EE, Latham TS, Songoro P, Charles M, Lane AC, Stuber SE, Makubi AN, Ware RE, Smart LR. Hydroxyurea with dose escalation for primary stroke risk reduction in children with sickle cell anaemia in Tanzania (SPHERE): an open-label, phase 2 trial. Lancet Haematol. 2023 Apr;10(4):e261-e271. doi: 10.1016/S2352-3026(22)00405-7. Epub 2023 Mar 1.

Reference Type: DERIVED

PMID: 36870358 (View on PubMed)

Other Identifiers

SPHERE

Identifier Type: -

Identifier Source: org_study_id