Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE)
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|ClinicalTrials.gov Identifier: NCT03948867|
Recruitment Status : Active, not recruiting
First Posted : May 14, 2019
Last Update Posted : December 9, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Anemia in Children||Drug: Hydroxyurea Diagnostic Test: Elevated Arm TCD Examination Diagnostic Test: Normal Arm TCD Examination||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||202 participants|
|Intervention Model:||Parallel Assignment|
|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|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||April 24, 2019|
|Estimated Primary Completion Date :||March 31, 2022|
|Estimated Study Completion Date :||March 31, 2022|
Experimental: 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.
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.
Experimental: 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.
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).
- Prevalence of Elevated TCD [ Time Frame: Baseline ]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
- Change in Primary Stroke Risk [ Time Frame: Up to 12 Months at Month 12 ]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.
- Laboratory and Clinical Correlates [ Time Frame: Up to 24 Months ]Identify laboratory and clinical correlates of elevated TCD velocities such as age, haemoglobin concentration, foetal haemoglobin, oxygen saturation, splenomegaly, history of acute chest syndrome, and previous malaria infection
- Change in Hemoglobin Concentration [ Time Frame: 6 Months ]For those receiving hydroxyurea, the change in hemoglobin between baseline hemoglobin and follow up hemoglobin when a participant has reached maximum tolerated dose of hydroxyurea.
- Effect of Splenomegaly and Malaria Infections [ Time Frame: Up to 24 Months ]Incidence of splenomegaly and malaria infection with rapid or laboratory malaria testing will be performed for any child presenting with fever. Incidence will be reported in the number of cases per 100 patient years. Abdominal ultrasound with splenic volume will be performed annually for all study participants. Quantify the degree of hypersplenism or autoinfarction and any association with malaria complications of SCA will be analyzed.
- Prevalence of Co-inherited G6PD and Alpha Thalassemia [ Time Frame: One time at Baseline ]DNA will be collected at baseline to determine the prevalence of co-inherited hematologic diseases such as G6PD and alpha thalassemia.
- Hydroxyurea Area Under the Curve (AUC) [ Time Frame: One time at 24 Months (Study Exit) ]For those receiving hydroxyurea, the AUC will be assessed after the patient has reached MTD.
- Single Nucleotide Polymorphisms Associated with Change in Percent Hemoglobin F on Hydroxyurea [ Time Frame: One Time at 24 Months (Study Exit) ]For those receiving hydroxyurea, we will identify single nucleotide polymorphisms that are associated with a greater change in hemoglobin F percent in response to hydroyxurea therapy.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||2 Years to 16 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03948867
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|Bugando Medical Centre|
|Responsible Party:||Children's Hospital Medical Center, Cincinnati|
|Other Study ID Numbers:||
|First Posted:||May 14, 2019 Key Record Dates|
|Last Update Posted:||December 9, 2021|
|Last Verified:||December 2021|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
Sickle Celll Anemia
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors