Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia
Information source: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hematologic Diseases; Anemia, Sickle Cell
Intervention: Hydroxyurea (Drug); Placebo (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI) Official(s) and/or principal investigator(s): Sherron Jackson, MD, Principal Investigator, Affiliation: Medical University of South Carolina James F. Casella, MD, Principal Investigator, Affiliation: Johns Hopkins University Lori Luchtman-Jones, MD, Principal Investigator, Affiliation: Children's Research Institute Rathi V. Iyer, MD, Principal Investigator, Affiliation: University of Mississippi Medical Center Scott T. Miller, MD, Principal Investigator, Affiliation: SUNY Health Science Center, Brooklyn Sohail R. Rana, MD, Principal Investigator, Affiliation: Howard University Zora R. Rogers, MD, Principal Investigator, Affiliation: University of Texas SW Medical Center Bruce W Thompson, Ph.D., Principal Investigator, Affiliation: Clinical Trials and Surveys Corp Julio Barredo, MD, Principal Investigator, Affiliation: University of Miami Medical Center Winfred C. Wang, MD, Study Chair, Affiliation: St. Jude Children's Research Hospital Courtney Thornburg, MD, Principal Investigator, Affiliation: Duke University Thomas Howard, MD, Principal Investigator, Affiliation: University of Alabama at Birmingham Lori Luck, MD, Principal Investigator, Affiliation: Drexel University R. Clark Brown, MD, PhD, Principal Investigator, Affiliation: Emory University Sharada Sarnaik, MD, Principal Investigator, Affiliation: Wayne State University
Summary
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.
Clinical Details
Official title: Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Primary outcome: 50% reduction in rates of damage to the major organs with surrogate markers of organ function
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
Minimum age: 9 Months.
Maximum age: 18 Months.
Gender(s): Both.
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
Locations and Contacts
University of Alabama at Birmingham, Birmingham, Alabama 35233, United States
Children's National Medical Center, Washington, District of Columbia 20010, United States
Howard University, Washington, District of Columbia 20060, United States
University of Miami, Miami, Florida 33136, United States
Emory University School of Medicine, Atlanta, Georgia 30342, United States
Johns Hopkins University, Baltimore, Maryland 21287, United States
Children's Hospital of Michigan/Wayne State Univ., Detroit, Michigan 48201, United States
University of Mississippi Medical Center, Jackson, Mississippi 39216, United States
SUNY Health Science Center, Brooklyn, Brooklyn, New York 11203, United States
Duke University Medical Center, Durham, North Carolina 27710, United States
Drexel University, Philadelphia, Pennsylvania 19134, United States
Medical University of South Carolina, Charleston, South Carolina 29425, United States
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
University of Texas SW Medical Center, Dallas, Texas 75390, United States
Additional Information
Related publications: Heeney MM, Whorton MR, Howard TA, Johnson CA, Ware RE. Chemical and functional analysis of hydroxyurea oral solutions. J Pediatr Hematol Oncol. 2004 Mar;26(3):179-84. Thompson BW, Miller ST, Rogers ZR, Rees RC, Ware RE, Waclawiw MA, Iyer RV, Casella JF, Luchtman-Jones L, Rana S, Thornburg CD, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik S, Howard TH, Luck L, Wang WC. The pediatric hydroxyurea phase III clinical trial (BABY HUG): challenges of study design. Pediatr Blood Cancer. 2010 Feb;54(2):250-5. doi: 10.1002/pbc.22269.
Starting date: August 2000
Last updated: April 15, 2011
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