Please select the eligibility criteria that correspond to the clinical trial below.
Title: Stroke Avoidance for Children in REpublica Dominicana (SACRED): A Prospective Research Study to Reduce Stroke in Children With Sickle Cell Anemia
Brief Summary: Prospective screening and treatment study for children with Sickle Cell Anemia and increased stroke risk living in the Dominican Republic.


Options:
A: Pediatric patients, ages 24 months to 16 years, with sickle cell anemia or S-beta zero thalassemia.
B: Inclusion Criteria:

* Pediatric participants with severe forms of sickle cell anemia (HbSS or HbSβ° thalassemia)
* Age: between 3.0 and 15.0 years at the time of enrollment
* Parent or guardian willing and able to provide informed consent
* Ability to comply with study related treatments, evaluations, and follow-up

There are no exclusion criteria applicable to the TCD screening portion of SACRED.

For participants with conditional TCD velocities, the following criteria will disqualify them from the treatment phase of SACRED:

Exclusion Criteria:

* Known medical condition making participation ill-advised (e.g., acute or chronic infectious disease including HIV, known allergy to hydroxyurea therapy, or malignancy)
* Abnormal historical laboratory values (most recent pre-enrollment values):

  1. Anemia: Hemoglobin concentration \< 6.0 gm/dL
  2. Reticulocytopenia: Absolute reticulocyte count \< 100 x 10˄9/L with a hemoglobin concentration \< 8.0 gm/dL
  3. Neutropenia: Absolute neutrophil count (ANC) \< 1.0 x 10˄9/L
  4. Thrombocytopenia: Platelet count \< 80 x10˄9 /L
  5. Known abnormal renal function (serum creatinine \>2X upper limit for age AND ≥ 1.0 mg/dL)
* Pregnancy (for post-menarchal females only)
C: Inclusion Criteria:

1. Pediatric participants with a severe form of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSD, HbSOArab)
2. Age: ≥ 2 and ≤ 17 years of age, at the time of enrollment
3. Time-averaged maximum velocity (TAMV) TCD Velocity in the conditional (170 - 199 cm/sec) or abnormal (≥200 cm/sec) range by Transcranial Doppler ultrasonography examination within 6 months of enrollment, abnormal or conditional TCD velocity and currently on commercial hydroxyurea for primary stroke prevention, or previously enrolled in SCATE, a previous stroke with abnormal or conditional TCD prior to stroke event.
4. Parent or guardian willing and able to provide informed consent and child gives assent
5. Ability to comply with study related treatments, evaluations, and follow- up visits

Exclusion Criteria:

1. Inability to take or tolerate daily oral hydroxyurea, including

   * Known allergy to hydroxyurea therapy
   * Known positive serology to HIV infection
   * Known malignancy
   * Current lactation
2. Abnormal historical laboratory values (most recent pre-enrollment values unless previously enrolled in SCATE):

   * Hemoglobin concentration \< 6.0 gm/dL
   * Absolute reticulocyte count \< 100 x 109/L with a hemoglobin concentration \< 8.0 gm/dL
   * White Blood Cell (WBC) count \< 3.0 x 109/L
   * Absolute neutrophil count (ANC) \< 1.0 x 109/L
   * Platelet count \< 100 x 109/L
3. Use of therapeutic agents for sickle cell disease (e.g., hydroxyurea, arginine, decitabine, magnesium, chronic transfusions) within 3 months of enrollment unless they have an abnormal TCD velocity and receive commercial hydroxyurea for primary stroke prevention or were previously enrolled in the SCATE study or for secondary stroke prevention in a child with a previous stroke.
4. Current participation in other therapeutic clinical trials, except SCATE
5. Known serum creatinine more than twice the upper limit for age AND

   * 1.0 mg/dL
6. Any condition or chronic illness, which in the opinion of the clinical investigator makes participation ill-advised
7. Pregnancy (for post-menarchal females only)
8. Erythrocyte transfusion within the past 2 months
9. Previous stem cell transplant or other myelosuppressive therapy (unless they have an abnormal TCD velocity and receive commercial hydroxyurea for primary stroke prevention or for secondary stroke prevention in a child with a previous stroke or were previously enrolled in SCATE)
D: INCLUSION:

* Patient must have sickle cell anemia (hemoglobin SS) or sickle beta thalassemia (hemoglobin SB) as confirmed at the local institution.
* Participating institutions must submit documentation of the diagnostic hemoglobin analysis to the Statistical and Clinical Coordinating Centers to confirm the diagnosis of sickle cell anemia prior to randomization.
* Patient must be 5 through 14 years of age.
* Patient must have a cerebral infarct documented by MRI scan as read by the neuroradiology panel.
* Informed consent with assent in accordance with the institutional policies (institutional Institutional Review Board approval) and Federal guidelines (approved by the United States Department of Health and Human Services) must be signed by the patient's legally authorized guardian acknowledging written consent to join the study. When suitable, patients will be requested to give their assent to join the study.

EXCLUSION:

* Patient with a history of a focal neurologic event lasting more than 24 hours with medical documentation or a history of prior overt stroke.
* Patients with a transcranial doppler (TCD) study with a time-averaged mean velocity greater than 200 cm/sec verified by the study radiologist.
* Patients with other neurological problems, such as neurofibromatosis, lead poisoning, or tuberous sclerosis.
* Patients with HIV infection.
* Pregnancy.
* Patients who received treatment with anti-sickling drugs or hydroxyurea within 3 months or anticipate receiving anti-sickling drugs or hydroxyurea during the course of the study.
* Abnormal kidney function (creatinine \> 2x upper limit of normal).
* Patients on chronic blood transfusion therapy for other reasons.
* Patients judged not likely to be compliant by his/her hematologist and local nurse coordinator based on previous compliance in clinic appointments and following advice. Specifically, families that have missed at least two appointments without notification within 12 months prior to the trial or parents of potential patients that have been reported for medical or education neglect are not eligible for this trial.
* Patients unable to receive blood transfusion because of alloimmunization.
* Patients with permanent or semi-permanent metallic (braces on teeth) structures attached to their body. Such patients cannot obtain a MRI of the head to assess the presence of silent cerebral infarcts.
* Siblings randomized in the trial.

Answer: B