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

NCT03948867 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: SPHERE
• Study Type: interventional
• Target: 202
• Locations: 2 countries
• Sites: 2

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.

Conditions

Sickle Cell Anemia in Children

Keywords

Sickle Celll Anemia; Transcranial Doppler; Tanzania; Hydroxyurea; Stroke

Outcome Measures

Primary Outcomes (2)

• Prevalence of Elevated TCD

  Determine 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

  Baseline

• Change in Primary Stroke Risk

  Transcranial Doppler ultrasound (TCD) will be used to measure the change in the TAMV of arterial blood flow in the 4 major intracranial arteries bilaterally from study enrollment to 12 months after study enrollment.

  Up to 12 Months at Month 12

Secondary Outcomes (6)

• Laboratory and Clinical Correlates

  Up to 24 Months

• Change in Hemoglobin Concentration

  6 Months

• Effect of Splenomegaly and Malaria Infections

  Up to 24 Months

• Prevalence of Co-inherited G6PD and Alpha Thalassemia

  One time at Baseline

• Hydroxyurea Area Under the Curve (AUC)

  One time at 24 Months (Study Exit)

Study Arms (2)

Elevated Initial Screening TCD

EXPERIMENTAL

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.

Drug: Hydroxyurea; Diagnostic Test: Elevated Arm TCD Examination

Normal Initial Screening TCD

EXPERIMENTAL

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.

Diagnostic Test: Normal Arm TCD Examination

Interventions

Hydroxyurea 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 Initial Screening TCD

Elevated Arm TCD Examination 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.

Elevated Initial Screening TCD

Normal Arm TCD Examination 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).

Normal Initial Screening TCD

Eligibility Criteria

• Age: 2 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Known medical condition making participation ill-advised.
• Known allergic reactions to components of hydroxyurea.
• Previous history of stroke.
• Currently pregnant or lactating.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Bugando Medical Centre: collaborator
• The American Society of Hematology: collaborator

Study Sites (2)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Bugando Medical Centre

Mwanza, Tanzania

Location

Related Publications (1)

• 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.

  PMID: 36870358 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The cohort will be divided into two arms based on the initial screening TCD result: 1) those who have a normal initial screening TCD and will be an observation/control cohort; and 2) 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

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: May 14, 2019
• Study Start: April 24, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 17, 2025

Record last verified: 2025-07

Locations

US (1); TA (1)