Stroke With Transfusions Changing to Hydroxyurea
Condition: Hemochromatosis; Cerebrovascular Accident; Anemia, Sickle Cell; Hematologic Diseases
MeSH terms: Stroke; Hematologic Diseases; Anemia, Sickle Cell; Hemochromatosis; Hemosiderosis
Intervention: Red Cell Transfusions; Iron Chelation; Hydroxyurea; Phlebotomy
Intervention description: Red Blood Cell Transfusions; Iron Chelation Therapy; Hydroxyurea; Phlebotomy
Intervention MeSH terms: Hydroxyurea
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 134.0
Sex: All
Minimum age: 5 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Blood Diseases

Summary:

      The purpose of this study is to compare standard therapy (transfusions and chelation) with
      alternative therapy (hydroxyurea and phlebotomy) for the prevention of secondary stroke and
      management of iron overload in children with sickle cell anemia (SCA).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia,
             HbSOArab)

          -  Age range of 5.0-18.9 years, inclusive, at the time of study entry

          -  Initial (primary) completed overt clinical stroke after the age of one year (12
             months) with documented infarction on brain computed tomography (CT) or magnetic
             resonance imaging (MRI)

          -  At least 18 months of chronic monthly erythrocyte transfusions since primary stroke

          -  Transfusional iron overload, defined as a previously documented liver iron
             concentration (LIC) greater than or equal to 5.0 mg Fe per gram of dry weight liver or
             serum ferritin greater than or equal to 500 ng/mL on two independent measurements

          -  Adequate monthly erythrocyte transfusions with average HbS less than or equal to 45%
             (the upper limit of the established academic community standard) in the 6 months prior
             to study entry

          -  Parent or guardian willing and able to provide informed consent with verbal or written
             assent from the child (less than 18 years of age) or subject willing and able to
             provide informed consent (older than 18 years of age)

          -  Ability to comply with study-related treatments, evaluations, and follow-up

        Exclusion Criteria:

          -  Inability to receive or tolerate chronic red blood cell (RBC) transfusion therapy, due
             to any of the following:

               1. Multiple RBC alloantibodies making cross-matching difficult or impossible

               2. RBC autoantibodies making cross-matching difficult or impossible

               3. Religious objection to transfusions that preclude their chronic use

               4. Non-compliance with transfusions in the 6 months prior to study entry (temporary
                  exclusion)

          -  Inability to take or tolerate daily oral hydroxyurea, due to any of the following:

               1. Known allergy to hydroxyurea therapy

               2. HIV infection

               3. Cancer

               4. Pregnant or breastfeeding

               5. Previous stem cell transplant or other myelosuppressive therapy

          -  Clinical and laboratory evidence of hypersplenism, due to any of the following:

               1. Palpable splenomegaly greater than 5 cm below the left costal margin and

               2. Transfusion requirement greater than 250 mL/kg in the 12 months prior to study
                  entry

          -  Abnormal laboratory values at initial evaluation (temporary exclusion):

               1. Pre-transfusion hemoglobin concentration less than 7.0 gm/dL

               2. White blood cell (WBC) count less than 3.0 x 109/L

               3. Absolute neutrophil count (ANC) less than 1.5 x 109/L

               4. Platelet count less than 100 x 109/L

               5. Serum creatinine more than twice the upper limit for age OR greater than or equal
                  to 1.0 mg/dL

          -  Current participation in other therapeutic clinical trials

          -  Current use of other therapeutic agents for SCA (e.g., arginine, decitabine,
             magnesium)

          -  Any condition or chronic illness, such as a positive tuberculin (PPD) test, which in
             the opinion of the study physician makes study participation ill-advised

          -  Inability or unwillingness to complete required screening studies, including blood
             tests, brain MRI/magnetic resonance angiography (MRA), and liver biopsy

          -  A sibling enrolled in SWiTCH