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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Anemia
• Intervention / Treatment: Drug: Hydroxyurea

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard University College of Medicine
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center Center for Cancer and Blood Disorders
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Emory University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore Alfred I Coplan Pediatric Hematology Oncology Outpatient Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan/Wayne State University
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New York
    • Brooklyn, New York, United States, 11203
      • Downstate Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center at Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Active; 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; Parents and child's doctor may plan to use or not to use hydroxyurea.
Passive; 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; Parents and child's doctor may plan to use or not to use hydroxyurea.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): December 31, 2016
• Study Completion (ACTUAL): December 31, 2016

Study Registration Dates

• First Submitted: February 1, 2013
• First Submitted That Met QC Criteria: February 4, 2013
• First Posted (ESTIMATE): February 5, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: HHSN268201200023C