- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03948867
Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE)
Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE): A Prospective Trial to Reduce Primary Stroke in Children With Sickle Cell Anaemia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Mwanza, Tanzania
- Bugando Medical Centre
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Ohio
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Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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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).
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.
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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).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Prevalence of Elevated TCD
Time Frame: Baseline
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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
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Baseline
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Change in Primary Stroke Risk
Time Frame: Up to 12 Months at Month 12
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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.
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Up to 12 Months at Month 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Laboratory and Clinical Correlates
Time Frame: Up to 24 Months
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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
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Up to 24 Months
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Change in Hemoglobin Concentration
Time Frame: 6 Months
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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.
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6 Months
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Effect of Splenomegaly and Malaria Infections
Time Frame: Up to 24 Months
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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.
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Up to 24 Months
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Prevalence of Co-inherited G6PD and Alpha Thalassemia
Time Frame: One time at Baseline
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DNA will be collected at baseline to determine the prevalence of co-inherited hematologic diseases such as G6PD and alpha thalassemia.
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One time at Baseline
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Hydroxyurea Area Under the Curve (AUC)
Time Frame: One time at 24 Months (Study Exit)
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For those receiving hydroxyurea, the AUC will be assessed after the patient has reached MTD.
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One time at 24 Months (Study Exit)
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Single Nucleotide Polymorphisms Associated with Change in Percent Hemoglobin F on Hydroxyurea
Time Frame: One Time at 24 Months (Study Exit)
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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.
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One Time at 24 Months (Study Exit)
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SPHERE
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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