Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies

A count of the number of patients enrolled will be provided.

Time frame: at baseline

Population: 58 subjects enrolled on study. Of those, n=7 came off study prior to randomization (N=2 came off study due to PI discretion, n=4 came off study due to Parent/guardian/patient choice, and n=1 was a screen failure (HBG)). The remaining n=51 were randomized.

A count of the number of patients randomized will be provided.

Time frame: Eight weeks (± 2 weeks) after study enrollment

Population: Fifty-one were randomized out of the 58 enrolled.

The number of patients who have successfully provided %HbF at baseline and study exit will be provided.

Time frame: At baseline and at completion of the protocol, up to 56 weeks after study enrollment

Population: N=42 patients completed the protocol therapy and had labs collected at exit visit.

Chronic medication compliance is defined based on medication possession ratio (MPR), a measure of the percentage of time that a patient has access to medication. Each participant's MPR is calculated as \[(days medication in family's possession/days prescribed medication) \* 100\].

Time frame: At completion of therapy, up to 56 weeks after study enrollment

Population: There were 51 subjects randomized to treatment of which 42 completed the protocol therapy. MPR was calculated on the full study period. The n=9 patients that were withdrawn were counted as \<80% chronic medical compliance. Of the n=42 patients that completed protocol treatment, n=41 had ≥80% chronic medication compliance.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

Change in PedsQL 4.0 score will be reported. Scores are based on a 100 point scale, 0-100 with higher scores indicating a better quality of life. We are taking the exit visit score and subtracting the baseline score.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Of the N=51 randomized patients (n=25 intensive arm and n=26 standard arm), only 1 patient had The PedsQL ™ Sickle Cell Disease Module data at both baseline and exit visit.

The total number of hospitalization events will be provided by arms. This analysis approach is different than what was written in the protocol due to small number of participants with hospitalizations and small number of hospitalization events.

Time frame: From baseline through completion of therapy, up to 56 weeks

Population: The n=51 subjects that were randomized to treatment.

Descriptive statistics of count and frequency will be provided for participants who were approached but refused to be enrolled on the study.

Time frame: Once, at enrollment

Population: n=154 subjects declined to participate in HUGKISS and provided the following reasons for declining to participate.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) N=41 of the 42 that completed the study had absolute neutrophil count (ANC) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) N=41 of the n=42 subjects that completed the study had absolute reticulocyte count (ARC) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) Of the 42 that completed the study, n=40 had bilirubin measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had Hemoglobin F (HbF) measurements at both baseline and at exit visit.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard arm.) N=42 subjects completed protocol therapy (n=23 to the intensive arm and n=19 to the standard arm.) All n=42 that completed the study had HGB measurements at both baseline and at exit visit.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) Of the 42 that completed the study, n=41 had lactate dehydrogenase (LDH) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had mean corpuscular volume (MCV) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had platelet (PLT) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had white blood cell (WBC) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) N=41 of the 42 that completed the study had absolute neutrophil count (ANC) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) N=41 of the n=42 subjects that completed the study had absolute reticulocyte count (ARC) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) Of the 42 that completed the study, n=40 had bilirubin measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had Hemoglobin F (Hbf) measurements at both baseline and at exit visit.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard arm.) N=42 subjects completed protocol therapy (n=23 to the intensive arm and n=19 to the standard arm.) All n=42 that completed the study had hemoglobin (HGB) measurements at both baseline and at exit visit.

Descriptive statistics of the change between baseline and completion of the study will be provided.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) Of the 42 that completed the study, n=41 had lactate dehydrogenase (LDH) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had mean corpuscular volume (MCV) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had platelet (PLT) measurements at both baseline and exit visits.

Descriptive statistics of the change between baseline and completion of the study will be provided and will be compared between two treatment arms using two sample t-test or exact Wilcoxon Rank Sum test depending on the normality of the data tested by the Shapiro-Wilk test.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Change calculations require subjects to have values at both baseline and exit visits. N=51 patients were randomized (n=25 to the Intensive arm and n=26 to the standard therapy arm.) N=42 subjects completed protocol therapy (n=23 in the intensive arm and n=19 in the standard arm.) All 42 that completed the study had white blood cell (WBC) measurements at both baseline and exit visits.

Normal TCD velocities will be defined as TCD velocities \<170 cm/s.

Time frame: From baseline at study entry to completion of therapy, up to 56 weeks

Population: Subjects that complete protocol therapy and have TCD ultrasound at exit visit. N=42 subjects completed protocol therapy.

Any operative procedure will be included.

Time frame: From start of therapy through completion of therapy, up to 56 weeks

Population: Includes all randomized patients, n=51.

Transfusion will be defined as the provision of red blood cells to correct anemia.

Time frame: From start of therapy through completion of therapy, up to 56 weeks

Population: Includes all randomized patients, n=51.

The number of patients with hospitalizations will be provided by arm. This analysis approach is different than what was written in the protocol due to small number of participants with hospitalizations and small number of hospitalization events.

Time frame: From baseline through completion of therapy, up to 56 weeks

Population: The n=51 subjects that were randomized to treatment.

Number of patients with toxicities to include: neutropenia (ANC \<1000\*/µL), reticulocytopenia (ARC \<80\*10\^3/µL and concomitant anemia (hemoglobin \<6 g/dL), and thrombocytopenia (platelets \<100\*10\^3/µL).

Time frame: From start of therapy through completion of therapy, up to 56 weeks

Population: N=51 randomized patients (n=25 intensive arm and n=26 standard arm).

Number of toxicities will be reported to include: neutropenia (ANC \<1000\*/µL), reticulocytopenia (ARC \<80\*10\^3/µL and concomitant anemia (hemoglobin \<6 g/dL), and thrombocytopenia (platelets \<100\*10\^3/µL).

Time frame: From start of therapy through completion of therapy, up to 56 weeks

Population: N=51 randomized patients (n=25 intensive arm and n=26 standard arm).