title: The pediatric hydroxyurea phase III clinical trial (BABY HUG): challenges of study design.
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).
authors.affiliation: Clinical Trials & Surveys Corp., Baltimore, Maryland 21117, USA. bthompson@c-tasc.com
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Thompson
authors.forename: Scott T
authors.initials: ST
authors.lastname: Miller
authors.forename: Zora R
authors.initials: ZR
authors.lastname: Rogers
authors.forename: Renee C
authors.initials: RC
authors.lastname: Rees
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
authors.forename: Myron A
authors.initials: MA
authors.lastname: Waclawiw
authors.forename: Rathi V
authors.initials: RV
authors.lastname: Iyer
authors.forename: James F
authors.initials: JF
authors.lastname: Casella
authors.forename: Lori
authors.initials: L
authors.lastname: Luchtman-Jones
authors.forename: Sohail
authors.initials: S
authors.lastname: Rana
authors.forename: Courtney D
authors.initials: CD
authors.lastname: Thornburg
authors.forename: Ram V
authors.initials: RV
authors.lastname: Kalpatthi
authors.forename: Julio C
authors.initials: JC
authors.lastname: Barredo
authors.forename: R Clark
authors.initials: RC
authors.lastname: Brown
authors.forename: Sharada
authors.initials: S
authors.lastname: Sarnaik
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Howard
authors.forename: Lori
authors.initials: L
authors.lastname: Luck
authors.forename: Winfred C
authors.initials: WC
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000188:drug therapy*; D000986:Antisickling Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D016903:Drug Monitoring; D023381:Endpoint Determination; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D000986:Antisickling Agents; D006918:Hydroxyurea