Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03948867|
Recruitment Status : Active, not recruiting
First Posted : May 14, 2019
Last Update Posted : December 9, 2021
|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.
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|