Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00006400
First received: October 12, 2000
Last updated: April 15, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Hematologic Diseases
Anemia, Sickle Cell
Drug: Hydroxyurea
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • 50% reduction in rates of damage to the major organs with surrogate markers of organ function [ Time Frame: Measured during follow-up evaluations ] [ Designated as safety issue: Yes ]

Enrollment: 191
Study Start Date: August 2000
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Participants will receive hydroxyurea.
Drug: Hydroxyurea
Participants will receive hydroxyurea.
Placebo Comparator: 2
Participants will receive placebo.
Drug: Placebo
Participants will receive placebo.

Detailed Description:

BACKGROUND:

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.

DESIGN NARRATIVE:

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.

  Eligibility

Ages Eligible for Study:   9 Months to 18 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006400

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
Howard University
Washington, District of Columbia, United States, 20060
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30342
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Michigan
Children's Hospital of Michigan/Wayne State Univ.
Detroit, Michigan, United States, 48201
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, New York
SUNY Health Science Center, Brooklyn
Brooklyn, New York, United States, 11203
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Drexel University
Philadelphia, Pennsylvania, United States, 19134
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
University of Texas SW Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Investigators
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
  More Information

Publications:
Wynn L, Miller S, Faughnan L, Luo Z, Debenham E, Fish B, Hustace T, Kelly T, MacDermott ML, Marasciulo J, Marshall J, Martin B, McDuffie J, Murphy M, Rackoff B, Reed C, Seaman P, Thomas G, Wang W. Recruitment of Infants with Sickle Cell Anemia to a Phase III Trial: Data from the BABY HUG Study. Contemp Clin Trials 2010; 31:558-563.
ZR Rogers, WC Wang, Z Luo, R Iyer, E Shalaby-Rana, S Dertinger, B Files, P Lane, B Thompson, ST Miller, RE Ware, BL Shulkin, JH Miller. Biomarkers of Splenic Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. Blood 2011; 117: 2614-2617

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Jonathan Goldsmith, MD, NHLBI
ClinicalTrials.gov Identifier: NCT00006400     History of Changes
Other Study ID Numbers: 89, N01 HB07150, N01 HB07151, N01 HB07152, N01 HB07153, N01 HB07154, N01 HB07155, N01 HB07156, N01 HB07157, N01 HB07158, N01 HB07159, N01 HB07160
Study First Received: October 12, 2000
Last Updated: April 15, 2011
Health Authority: United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Blood Diseases
Sickle Cell Anemia

Additional relevant MeSH terms:
Anemia
Anemia, Sickle Cell
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014