Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) Follow-up Observational Study II Protocol

Study Overview
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Brief Summary
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The BABY HUG Treatment Study was designed to see if treatment with the drug hydroxyurea (also called HU) in children with sickle cell disease could prevent organ damage, especially in the spleen and kidneys. There was also a chance that treatment could prevent painful crises, lung disease, stroke, and blood infection.

Detailed Description
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The current observational trial, Follow-Up Study ((FUS) II includes enhanced neuropsychological, brain, cardiac, and pulmonary evaluations for this very well characterized cohort of subjects. Measures of spleen and renal function and markers of DNA damage will continue to be collected. Assessment of other target organs in sickle cell disease including pulmonary and cardiac function will be performed in addition to evaluation of developmental aspects of sickle cell disease (SCD) and potential HU toxicity.

Official Title
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Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) Follow-up Observational Study II Protocol

Conditions
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Sickle Cell Anemia

Intervention / Treatment
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* Drug: Hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects enrolled in the BABY HUG Follow-Up I Study who participated for at least 24 months are eligible for the Follow-Up Study II Exclusion Criteria: Subjects that have received a Stem Cell Transplant are not eligible for enrollment

Ages Eligible for Study
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Minimum Age: 24 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active<br>Complete blood counts (CBCs), reticulocytes, differential, lactate dehydrogenase (LDH), bilirubin and alanine transaminases (ALTs), cystatin C, blood urea nitrogen (BUN), Creatinine, fetal hemoglobin (HbF), pit counts, Howell Jolly Body (HJB), and urine microalbumin:creatinine ratio were collected at study entry, annually, and exit to Follow-Up Study II. Variable-diversity-joining (VDJ) and a stored blood sample were collected at study entry and study exit. Additional tests that include liver/spleen scan, abdominal sonogram, pulmonary function testing, magnetic resonance imaging (MRI) / magnetic resonance angiography (MRA), cardiac echocardiogram, or neuropsychology testing were collected once during the study when the child was 10 years old. | Drug: Hydroxyurea<br>* Parents and child's doctor may plan to use or not to use hydroxyurea.<br>|
| Passive<br>Complete blood counts (CBCs), reticulocytes, differential, lactate dehydrogenase (LDH), bilirubin and alanine transaminases (ALTs), cystatin C, blood urea nitrogen (BUN), Creatinine, fetal hemoglobin (HbF), pit counts, Howell Jolly Body (HJB), variable-diversity-joining (VDJ), urine microalbumin:creatinine ratio and a stored blood sample were collected at study entry and exit to Follow-Up Study II. Additional tests that include liver/spleen scan, abdominal sonogram, pulmonary function testing, MRI/MRA, cardiac echocardiogram, or neuropsychology testing were collected as part of clinical care. | Drug: Hydroxyurea<br>* Parents and child's doctor may plan to use or not to use hydroxyurea.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | The change in splenic function from the randomized control trial baseline measurement was one of the primary outcomes. The change in splenic function (worse vs not-worse) was compared between the randomized treatment groups (hydroxyurea vs placebo). The change in splenic function from baseline (before treatment initiation) to age 10 years (a visit when child turned 10 years old) was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, decreased to normal, absent to absent, or absent to decreased. | baseline and when child turned 10 years old | 
| Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | The change in splenic function from the randomized control trial baseline measurement was one of the primary outcomes. The change in splenic function (worse vs not-worse) was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. The change in splenic function from baseline (before treatment initiation) to age 10 years (a visit when child turned 10 years old) was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, decreased to normal, absent to absent, or absent to decreased. | baseline and when child turned 10 years old | 
| Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | The change in the percentage of pitted cell from randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between the randomized treatment groups (hydroxyurea vs placebo). | Baseline and End of follow-up II study (up to 13 years from randomization date) | 
| Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit | The change in the percentage of pitted cell from the randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. | Baseline and End of follow-up II study (up to 13 years from randomization date) | 
| Change in Howell Jolly Body (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo | The change in Howell Jolly Body from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell Jolly Body was compared between the randomized treatment groups (hydroxyurea vs placebo). | Baseline and End of follow-up II study (up to 13 years from randomization date) | 
| Change in Howell Jolly Body (HJB) Count From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea | The change in Howell Jolly Body count from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. | Baseline and End of follow-up II study (up to 13 years from randomization date) |