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).

journal_name

Pediatr Blood Cancer

journal_title

Pediatric blood & cancer

authors

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

doi

10.1002/pbc.22269

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

250-5

issue

2

eissn

1545-5009

issn

1545-5017

journal_volume

54

pub_type

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