Sickle Cell Disease - Stroke Prevention in Nigeria Trial

• Status: Completed
• Trial end date: 2019-01-31
• Target enrollment: 0
• Participant gender: All

Summary

Given large absolute numbers of individuals with sickle cell disease in Nigeria, hydroxyurea therapy for all individuals with sickle cell disease may not be initially feasible; however, a targeted strategy of hydroxyurea use for primary prevention of strokes is an alternative to the standard therapy (observation) for high-risk individuals. The investigators propose a feasibility study, Sickle Cell Disease - Stroke Prevention in Nigeria (SPIN) Trial, to determine whether hydroxyurea can be used for primary prevention of strokes in Nigerian children with sickle cell anemia.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University; Vanderbilt University Medical Center
• Collaborators: Aminu Kano Teaching Hospital; Barau Dikko Teaching Hospital/Kaduna State University; National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH)
• Treatments: Hydroxyurea

Criteria

Inclusion Criteria for Screening:

• Patients with hemoglobin SS or S beta zero thalassemia confirmed by hemoglobin electrophoresis;

• Informed consent from a parent or legal guardian and assent of participant ages 5 through 12;

• Successful completion of screening procedures: cerebral blood flow velocity ≥ 200 cm/sec in the terminal portion of the middle cerebral artery;

• Patient must be 5 through 12 years of age (i.e., must have attained their 5th but not their 13th birthday when the consent is signed).

Exclusion Criteria for Screening:

• Prior overt stroke (a focal neurological deficit of acute onset) by history, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive "10 questions" screening (an established tool in resource poor countries).(2,3) A "positive" screening is defined as answering yes to any one of the 10 questions. The negative predictive value (child does not have moderate or several neurological impairment) of the "10 questions" is greater than 94% in children (2);

• Other exclusions: significant cytopenias [absolute neutrophil count (ANC) <1500/ul, platelets <150,000/ul, reticulocytes <80,000/ul, unless Hb is > 9 g/dl], renal insufficiency (creatinine > 0.8 mg/dl); other significant organ system dysfunction, or other contraindication to hydroxyurea therapy; and history of seizures or diagnosis of epilepsy;

• Patients for whom hydroxyurea therapy is under consideration prior to study consent/education;

• Patients who have previously been treated with hydroxyurea and are being considered to restart hydroxyurea therapy;

• Other significant organ system dysfunction;

• Any other condition or chronic illness, which in the opinion of the site's Principal Investigator (PI) makes participation ill-advised or unsafe.

• Participants of child bearing age who are pregnant or may become pregnant should not take hydroxyurea. If a participant becomes pregnant during the study, their hydroxyurea treatment will be stopped immediately. The onsite will notify the clinical coordinating center and the principal investigators of the case. The site principal investigator and study principal investigators will determine what therapy the participant should receive during pregnancy that is of standard care.

Inclusion Criteria for Study Therapy:

• Successful completion of screening procedures inclusive of cerebral blood flow velocity greater than or equal to 200 cm/sec measured twice or at least one measurement greater than or equal to 220 cm/sec in the terminal portion of the middle cerebral artery or two TCD measurements above 190 cm/sec within a three month interval;

• Informed consent from a parent or legal guardian for study therapy and assent of the participant completed;

• Participant is able to swallow a capsule as observed by study personnel;

• Acceptance of hydroxyurea therapy for one year. After one year of therapy, the participant will have the option to continue therapy with follow up visits to monitor adherence to therapy.

Exclusion Criteria for Treatment Group:

• Unable to commit to follow up visits for the course of the study.

Inclusion Criteria for participants that are not eligible to receive hydroxyurea therapy, but will be followed for one year (control group):

• Successful completion of screening procedures inclusive of cerebral blood flow velocity less than or equal to 199 cm/sec in the terminal portion of the middle cerebral artery;

• Informed consent from a parent or legal guardian and assent from the participant;

• Acceptance to be followed for one year in the study. Hydroxyurea may be given for other reasons as part of the participant's ongoing care, but it will not be given as part of the study.

Exclusion Criteria for the treatment and control groups:

• Unable to commit to follow up visits for the course of the study.