Hydroxyurea to Prevent Organ Damage in Children With Sickle Cell Anemia - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00006400

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 III

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Anemia Sickle Cell Anemia

Drug Information available for: Hydroxyurea

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Pediatric Hydroxyurea in Sickle Cell Anemia (BABY HUG)

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 ]

Estimated Enrollment:	200
Study Start Date:	August 2000
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Participants will receive hydroxyurea.	Drug: Hydroxyurea Participants will receive hydroxyurea.
2: Placebo Comparator 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, District of Columbia
Children's Research Institute
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, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
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, 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

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:	Julio Barredo, MD	Medical University of South Carolina
Study Chair:	James F. Casella, MD	Johns Hopkins University
Study Chair:	Caterina Minnetti, MD	Children's Research Institute
Study Chair:	Rathi V. Iyer, MD	University of Mississippi Medical Center
Study Chair:	Scott T. Miller, MD	SUNY Health Science Center, Brooklyn
Study Chair:	Sohail R. Rana, MD	Howard University
Study Chair:	Zora R. Rogers, MD	University of Texas SW Medical Center
Study Chair:	Bruce Thompson	Clinical Trials and Surveys Corporation
Study Chair:	Stuart Toledano, MD	University of Miami
Study Chair:	Winfred C. Wang, MD	St. Jude Children's Research Hospital
Study Chair:	Sherri A. Zimmerman, MD	Duke University

More Information

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.

Responsible Party:	Howard University ( Sohail R. Rana, MD )
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:	October 14, 2008
ClinicalTrials.gov Identifier:	NCT00006400
Health Authority:	United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Blood Diseases
Sickle Cell Anemia

Study placed in the following topic categories:

Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hydroxyurea
Hematologic Diseases
Hemoglobinopathies

Anemia
Anemia, Hemolytic
Hemoglobinopathy
Anemia, Sickle Cell
Sickle cell anemia

Additional relevant MeSH terms:

Antisickling Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Hematologic Agents
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009