Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE): A Prospective Trial to Reduce Primary Stroke in Children With Sickle Cell Anaemia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 202
- 试验地点
- 2
- 主要终点
- Prevalence of Elevated TCD
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Elevated Arm TCD Examination (Diagnostic Test)
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.
干预措施: Normal Arm TCD Examination (Diagnostic Test)
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.
干预措施: Hydroxyurea (Drug)
结局指标
主要结局
Prevalence of Elevated TCD
时间窗: 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
时间窗: 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.
次要结局
- Effect of Splenomegaly and Malaria Infections(Up to 24 Months)
- Hydroxyurea Area Under the Curve (AUC)(One time at 24 Months (Study Exit))
- Single Nucleotide Polymorphisms Associated with Change in Percent Hemoglobin F on Hydroxyurea(One Time at 24 Months (Study Exit))
- Laboratory and Clinical Correlates(Up to 24 Months)
- Change in Hemoglobin Concentration(6 Months)
- Prevalence of Co-inherited G6PD and Alpha Thalassemia(One time at Baseline)