Therapeutic Response Evaluation and Adherence Trial (TREAT)

There is now ample clinical evidence that hydroxyurea is a safe and effective medication for
adults and children with sickle cell anemia (SCA), and most hematologists agree the
short-term safety and efficacy of hydroxyurea has been proven. The National Heart, Lung, and
Blood Institute have recently released evidence-based guidelines for SCA, recommending that
hydroxyurea be offered to all affected children as young as nine months of age, regardless of
clinical severity. Despite the overwhelming evidence demonstrating safety and efficacy,
hydroxyurea remains underutilized for a variety of reasons. In this prospective study, the
investigators will utilize innovative strategies designed to address and overcome some of the
barriers that currently limit the use of hydroxyurea for children with SCA. The investigators
will utilize novel laboratory techniques and pharmacometric modeling in order to accurately
predict the most effective hydroxyurea dose referred to as the maximum tolerated dose. The
investigators aim to develop a screening urine test to objectively and accurately determine
adherence to hydroxyurea therapy. In addition, the study will document critical laboratory
and clinical characteristics of this unique population of patients with SCA who begin
hydroxyurea at a young age.

This study will follow two groups of patients. The first group, referred to as the New
Cohort, will include mostly young infants who are not receiving hydroxyurea therapy upon
entering the study. The starting dose of hydroxyurea for each of the participants in the New
Cohort will be individually determined using the novel population PK/PD dose-prediction
model. The second group of study participants, referred to as the Old Cohort, will include
patients who are already receiving hydroxyurea therapy upon study entry. Both the Old and New
Cohort (New Cohort) will be included in the development of a urine biomarker of adherence and
will be followed throughout the study to document the effect hydroxyurea has upon organ
function and quality of life. It is important to note that this is not a therapeutic drug
trial. Prior to enrollment in the study, participants, along with their families and clinical
providers, have decided to initiate hydroxyurea therapy for clinical indications. Except for
the dose prediction model for the New Cohort, participants will be treated and monitored
according to the routine clinical practice guidelines of the Cincinnati Children's Hospital
Comprehensive Sickle Cell Center.

Inclusion Criteria:

1. Diagnosis of sickle cell anemia (HbSS or Hbβ0-thalassemia)

2. Age 6 months to 21 years at the time of enrollment

3. Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea
therapy, including patients who are transitioning from chronic transfusions to
hydroxyurea therapy

Exclusion Criteria:

1. Family unwillingness to sign informed consent or comply with study treatments