The pediatric hydroxyurea phase III clinical trial (BABY HUG): Challenges of study design |
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Authors: | Bruce W. Thompson PhD Scott T. Miller MD Zora R. Rogers MD Renee C. Rees PhD Russell E. Ware MD PhD Myron A. Waclawiw PhD Rathi V. Iyer MD James F. Casella MD Lori Luchtman‐Jones MD Sohail Rana MD Courtney D. Thornburg MD Ram V. Kalpatthi MD Julio C. Barredo MD R. Clark Brown MD PhD Sharada Sarnaik MD Thomas H. Howard MD Lori Luck MD Winfred C. Wang MD |
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Affiliation: | 1. Clinical Trials & Surveys Corp., Baltimore, Maryland;2. SUNY—Downstate Medical Center/Kings County Hospital Center, Brooklyn, New York;3. UT Southwestern Medical Center, Dallas, Texas;4. St. Jude Children's Research Hospital, Memphis, Tennessee;5. National Heart, Lung, and Blood Institute, Bethesda, Maryland;6. University of Mississippi Medical Center, Jackson, Mississippi;7. Johns Hopkins University, Baltimore, Maryland;8. Children's National Medical Center, Washington, District of Columbia;9. Howard University, Washington, District of Columbia;10. Duke University Medical Center, Durham, North Carolina,;11. Medical University of South Carolina, Charleston, South Carolina;12. University of Miami, Miami, Florida;13. Emory University, Atlanta, Georgia;14. Children's Hospital of Michigan, Detroit, Michigan;15. University of Alabama‐Birmingham, Birmingham, Alabama;16. Drexel University, Philadelphia, Pennsylvania |
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Abstract: | Evidence of the laboratory benefits of hydroxyurea and its clinical efficacy in reducing acute vaso‐occlusive events in adults and children with sickle cell anemia has accumulated for more than 15 years. A definitive clinical trial showing that hydroxyurea can also prevent organ damage might support widespread use of the drug at an early age. BABY HUG is a randomized, double‐blind placebo‐controlled trial to test whether treating young children ages 9–17 months at entry with a liquid preparation of hydroxyurea (20 mg/kg/day for 2 years) can decrease organ damage in the kidneys and spleen by at least 50%. Creation of BABY HUG entailed unique challenges and opportunities. Although protection of brain function might be considered a more compelling endpoint, preservation of spleen and renal function has clinical relevance, and significant treatment effects might be discernable within the mandated sample size of 200. Concerns about unanticipated severe toxicity and burdensome testing and monitoring requirements were addressed in part by an internal Feasibility and Safety Pilot Study, the successful completion of which was required prior to enrolling a larger number of children on the protocol. Concerns over recruitment of potentially vulnerable subjects were allayed by inclusion of a research subject advocate, or ombudsman. Finally, maintenance of blinding of research personnel was aided by inclusion of an unblinded primary endpoint person, charged with transmitting endpoint data and monitoring blood work locally for toxicity (ClinicalTrials.gov number, NCT00006400). Pediatr Blood Cancer 2010;54:250–255. © 2009 Wiley‐Liss, Inc. |
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Keywords: | clinical trial hydroxyurea infants sickle cell |
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