Sparing Conversion to Abnormal TCD (Transcranial Doppler) Elevation (SCATE)
Condition: Sickle Cell Anemia
MeSH terms: Anemia; Anemia, Sickle Cell
Intervention: Hydroxyurea
Intervention description: Hydroxyurea will be administered once daily, in either capsule form (300mg, 400mg, or 500mg) or as a liquid formulation (100mg/ml). Dosing will commence at 20 mg/kg/day. Dose escalation will occur in 5 mg/kg/day increments, adjusting every 8 weeks unless hematological toxicity occurs.
Intervention MeSH terms: Hydroxyurea
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 2 Years
Maximum age: 10 Years
Healthy volunteers: No
Keywords: Phase III; Sickle cell anemia; Conditional transcranial doppler velocities; Reduce risk of conversion to abnormally high transcranial doppler velocities; Pediatric patients

Summary:

      The primary goal of the Phase III SCATE trial is to compare 30 months of alternative therapy
      (hydroxyurea) to standard care (observation) in children with sickle cell anemia and
      conditional (170 - 199cm/sec) Transcranial Doppler (TCD) velocities. For the alternative
      regimen (hydroxyurea) to be declared superior to the standard treatment regimen
      (observation), the hydroxyurea-treated group must have a three-fold reduction in the
      incidence of conversion to abnormal TCD velocities (≥ 200 cm/sec), compared to the standard
      treatment arm.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia,
             HbSD, HbSOArab)

          2. Age: ≥ 2 and < 11 years of age, at the time of enrollment

          3. Conditional TCD Velocity (170 - 199cm/sec) by Transcranial Doppler ultrasonography
             examination within 3 months of enrollment

          4. Parent or guardian willing and able to provide informed consent

          5. Ability to comply with study related treatments, evaluations, and follow-up

        Exclusion Criteria:

          1. Prior abnormal TCD Velocity

          2. History of clinical stroke

          3. Inability to take or tolerate daily oral hydroxyurea, including

               -  Known allergy to hydroxyurea therapy

               -  Known positive serology to HIV infection

               -  Known malignancy

               -  Current lactation

          4. Abnormal laboratory values at initial evaluation (temporary exclusions):

               -  Hemoglobin concentration < 6.0 gm/dL

               -  Absolute reticulocyte count < 100 x 10^9/L with a hemoglobin concentration < 8.0
                  gm/dL

               -  WBC count < 3.0 x 10^9/L

               -  Absolute neutrophil count (ANC) < 1.0 x 10^9/L

               -  Platelet count < 100 x 10^9/L

          5. Current use of therapeutic agents for sickle cell disease (e.g., hydroxyurea,
             arginine, decitabine, magnesium, chronic transfusions). Subjects must be off
             therapeutic agents for sickle cell disease for at least 3 months prior to enrollment.

          6. Current participation in other therapeutic clinical trials

          7. Serum creatinine more than twice the upper limit for age OR ≥ 1.0 mg/dL

          8. Any condition or chronic illness, which in the opinion of the clinical investigator
             makes participation ill-advised

          9. Pregnancy (for post-menarchal females only)

         10. Erythrocyte transfusion within the past 2 months

         11. Previous stem cell transplant or other myelosuppressive therapy