Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00006400
Recruitment Status : Completed
First Posted : October 13, 2000
Last Update Posted : April 27, 2011
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)

October 12, 2000
October 13, 2000
April 27, 2011
August 2000
September 2009   (Final data collection date for primary outcome measure)
50% reduction in rates of damage to the major organs with surrogate markers of organ function [ Time Frame: Measured during follow-up evaluations ]
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Complete list of historical versions of study NCT00006400 on Archive Site
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Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia
Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)
The purpose of this study is to determine if hydroxyurea therapy is effective in the prevention of chronic end organ damage in pediatric patients with sickle cell anemia.


In 1995, the Multicenter Study of Hydroxyurea (MSH) demonstrated that hydroxyurea is effective in decreasing the frequency of painful crises, hospitalizations for crises, acute chest syndrome, and blood transfusions by 50%. The recently completed phase II study of hydroxyurea in children (PED HUG) demonstrated that children have a response to hydroxyurea similar to that seen in adults in terms of increasing fetal hemoglobin levels and total hemoglobin, and decreasing complications associated with sickle cell anemia. In addition, this study demonstrated that the drug does not adversely affect growth and development between the ages of 5 and 15. A recently completed pilot study of hydroxyurea given to children between the ages of 6 months and 24 months demonstrated that the drug is tolerated well by small infant, and that the fetal hemoglobin switch can be forced to remain in the "on position" by hydroxyurea administration.

A Special Emphasis Panel (SEP) met on April 12, 1996 to review the results of the MSH trial and the progress to date of the PED HUG study. The SEP recommended that NHLBI undertake the BABY HUG trial.


BABY HUG is a randomized, double-blind, placebo-controlled study to determine if hydroxyurea can prevent the onset of chronic end organ damage in young children with sickle cell anemia. Approximately 200 children with sickle cell disease will be recruited to receive either hydroxyurea or placebo. The children will be screened at study entry for signs of abnormal brain, kidney, pulmonary, and splenic function, and developmental milestones. They will then be randomly assigned to receive either hydroxyurea or placebo and followed yearly to assess chronic end organ damage of the major organ systems. The primary endpoint will be a 50% reduction in rates of damage to the major organs with surrogate markers of organ function during follow-up in Phase II of the trial.

Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
  • Hematologic Diseases
  • Anemia, Sickle Cell
  • Drug: Hydroxyurea
    Participants will receive hydroxyurea.
  • Drug: Placebo
    Participants will receive placebo.
  • Active Comparator: 1
    Participants will receive hydroxyurea.
    Intervention: Drug: Hydroxyurea
  • Placebo Comparator: 2
    Participants will receive placebo.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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September 2009
September 2009   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Majority fetal and sickle (FS or SF) hemoglobin pattern confirmed centrally by electrophoresis (screening may begin at 7 months of age)

Exclusion Criteria:

  • Chronic transfusion therapy
  • Cancer
  • Less than 5th percentile (10th percentile for the pilot study) height, weight, or head circumference for age
  • Severe developmental delay (e.g., cerebral palsy or other mental retardation, Grade III/IV intraventricular hemorrhage)
  • Stroke with neurological deficit
  • Surgical splenectomy
  • Participating in other clinical intervention trials
  • Probable or known diagnosis of Hemoglobin S-Hereditary Persistence of Fetal Hemoglobin
  • Known hemoglobin S-beta plus thalassemia (hemoglobin A present)
  • Any condition or chronic illness, which in the opinion of the principal investigator, makes participation unadvised or unsafe
  • Inability or unwillingness to complete baseline (pre-enrollment) studies, including blood or urine specimen collection, liver-spleen scan, abdominal sonogram, neurological examination, neuropsychological testing, or transcranial Doppler ultrasound (interpretable study not required, but confirmed velocity greater than 200 cm/sec results in ineligibility)
  • Previous or current treatment with hydroxyurea (HU) or another anti-sickling drug
  • The following exclusion criteria are transient; patients can be re-evaluated for eligibility:

    1. Hemoglobin less than 6.0 gm/dL
    2. Reticulocyte count less than 80,000/cu mm if hemoglobin is less than 9 gm/dL
    3. Neutrophil count less than 2,000/cu mm
    4. Platelet count less than 130,000/cu mm
    5. Blood transfusion in the 2 months prior to study entry unless HbA is less than 10%
    6. ALT greater than twice the upper limit of normal
    7. Ferritin less than 10 ng/ml
    8. Serum creatinine greater than twice the upper limit of normal for age
    9. Bayley standardized mental score below 70
Sexes Eligible for Study: All
9 Months to 18 Months   (Child)
Contact information is only displayed when the study is recruiting subjects
United States
N01 HB07150
N01 HB07151
N01 HB07152
N01 HB07153
N01 HB07154
N01 HB07155
N01 HB07156
N01 HB07157
N01 HB07158
N01 HB07159
N01 HB07160
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Jonathan Goldsmith, MD, NHLBI
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Sherron Jackson, MD Medical University of South Carolina
Principal Investigator: James F. Casella, MD Johns Hopkins University
Principal Investigator: Lori Luchtman-Jones, MD Children's Research Institute
Principal Investigator: Rathi V. Iyer, MD University of Mississippi Medical Center
Principal Investigator: Scott T. Miller, MD SUNY Health Science Center, Brooklyn
Principal Investigator: Sohail R. Rana, MD Howard University
Principal Investigator: Zora R. Rogers, MD University of Texas SW Medical Center
Principal Investigator: Bruce W Thompson, Ph.D. Clinical Trials and Surveys Corp
Principal Investigator: Julio Barredo, MD University of Miami Medical Center
Study Chair: Winfred C. Wang, MD St. Jude Children's Research Hospital
Principal Investigator: Courtney Thornburg, MD Duke University
Principal Investigator: Thomas Howard, MD University of Alabama at Birmingham
Principal Investigator: Lori Luck, MD Drexel University
Principal Investigator: R. Clark Brown, MD, PhD Emory University
Principal Investigator: Sharada Sarnaik, MD Wayne State University
National Heart, Lung, and Blood Institute (NHLBI)
April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP