Clinical trial NCT03948867: Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE)
Official title: Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE): A Prospective Trial to Reduce Primary Stroke in Children With Sickle Cell Anaemia
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Sickle Cell Anemia in Children
Keywords: Sickle Celll Anemia
Transcranial Doppler
Tanzania
Hydroxyurea
Stroke
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Bugando Medical Centre
name: The American Society of Hematology
First posted: 2019-05-14
Enrollment: 202
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.

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:

There are no permanent exclusion criteria for participants to enroll in the screening TCD portion of SPHERE. Temporary, time-limited exclusion criteria for the screening TCD portion include the following:

* 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.

Primary outcomes:
measure: Prevalence of Elevated TCD
timeFrame: Baseline
measure: Change in Primary Stroke Risk
timeFrame: Up to 12 Months at Month 12
Secondary outcomes:
measure: Laboratory and Clinical Correlates
timeFrame: Up to 24 Months
measure: Change in Hemoglobin Concentration
timeFrame: 6 Months
measure: Effect of Splenomegaly and Malaria Infections
timeFrame: Up to 24 Months
measure: Prevalence of Co-inherited G6PD and Alpha Thalassemia
timeFrame: One time at Baseline
measure: Hydroxyurea Area Under the Curve (AUC)
timeFrame: One time at 24 Months (Study Exit)
measure: Single Nucleotide Polymorphisms Associated with Change in Percent Hemoglobin F on Hydroxyurea
timeFrame: One Time at 24 Months (Study Exit)
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Mwanza
country: Tanzania
facility: Bugando Medical Centre
Study officials:
References: