Please select the eligibility criteria that correspond to the clinical trial below.
Title: Hydroxyurea Optimization Through Precision Study (HOPS): A Prospective, Multi-center, Randomized Trial of Personalized, Pharmacokinetics-guided Dosing of Hydroxyurea Versus Standard Weight-based Dosing for Children With Sickle Cell Anemia.
Brief Summary: Hydroxyurea Optimization through Precision Study (HOPS) is a prospective, multi-center, randomized trial that will directly compare a novel, individualized dosing strategy of hydroxyurea to standard weight-based dosing for children with SCA. The primary objective of the study is to evaluate whether a pharmacokinetics-based starting hydroxyurea dose thieves superior fetal hemoglobin response to to standard weight-based initial dosing. Patients will be recruited from the pediatric sickle cell clinic at Cincinnati Children's Hospital Medical Center and from additional pediatric sickle cell centers within the United States.


Options:
A: Inclusion Criteria:

* 1)Diagnosis of HbSS, or HbSβ-thalassemia0, confirmed by hemoglobin analysis
* 2)Males and females age 16 years to 70 years old
* 3)Greater than 2 episodes of pain in the last 12 months
* 4)On a stable dose of hydroxyurea for at least 2 months and a stable hemoglobin

Exclusion Criteria:

1. Judged not likely to be study compliant by his/her hematologist
2. History of adverse reaction to montelukast or any of the components of montelukast
3. Have used medications known to interact with montelukast such as rifampin, phenobarbital, and gemfibrozil within 4 weeks of enrollment
4. Currently being treated with a leukotriene antagonist (montelukast or zileuton) or have used montelukast/zileuton within the last 60 days
5. Chronic blood transfusion therapy defined as regularly scheduled transfusions.
6. Hemoglobin A greater than15% on hemoglobin analysis
7. Individuals with a current physician diagnosis of asthma (within last 12 months) or requires continuous supplemental oxygen, or predicted or current use of asthma medications (inhaled corticosteroids, but participants taking bronchodilators will be allowed to participate).
8. Current participation in another therapeutic trial for SCD
9. Known current pregnancy
10. Known history of HIV
11. Serum creatinine greater than 3 times the site's upper limit of normal
B: Inclusion Criteria:

* Diagnosis of HbSC disease
* Hemoglobin level between 8 and 12.5 g/dL
* At least one vaso-occlusive event (e.g., pain, acute chest syndrome) in the 12 months prior to study entry. An episode of pain is defined as the occurrence of pain in the extremities, back, abdomen, chest, or head that lasts at least 2 hours; requires a visit to a hospital, emergency room, clinic, or provider's office; and is not explained except by SCD. Acute chest syndrome is defined as a new pulmonary infiltrate on a chest x-ray associated with a fever (greater than 38.5° C), tachypnea, wheezing, cough, or chest pain.
* Regular compliance with comprehensive care
* In a steady disease state and not experiencing an acute complication of SCD (i.e., no hospitalization, pain event, or episode of acute chest syndrome within the 1 month prior to study entry)

Exclusion Criteria:

* Previous transfusion with remaining hemoglobin A greater than 10%
* Previous treatment with hydroxyurea within the last 3 months
* Previous treatment with magnesium within the 3 months prior to study entry (including vitamins containing magnesium)
* Poor compliance with previous treatment regimens
* Liver dysfunction (SGPT greater than twice the upper limit of normal) within the 1 month prior to study entry
* Kidney dysfunction (creatinine greater than or equal to 1.0 mg/dL for participants less than 18 years of age; greater than or equal to 1.2 mg/dL for participants 18 years of age or older) within the 1 month prior to study entry
* Pregnant
* Ten or more hospital admissions for pain in the 12 months prior to study entry
* Daily use of narcotics
* Treatment with any investigational drug in the 3 months prior to study entry
* Less than 3% red blood cells with density greater than 41 g/dL (as measured by the ADVIA 120 system)
* Positive HIV test
* Other long-term illness or disorder other than SCD that could adversely affect performance in the study (e.g., tuberculosis)
C: 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
D: Inclusion Criteria:

* Diagnosis of sickle cell anemia (HbSS, HbSD, HbS/β0-thalassemia, or similarly severe SCA genotype)
* Age 6 months to 21 years at the time of enrollment
* Clinical decision by patient, family, and healthcare providers to initiate hydroxyurea therapy

Exclusion Criteria:

* Current treatment with chronic, monthly blood transfusions or erythrocytapheresis
* Treatment with hydroxyurea within the past 3 months
* Hemoglobin SC disease, HbS/β+-thalassemia
* Current treatment with other investigational sickle cell medications
* Current known pregnancy or lactation

Answer: D