The pediatric hydroxyurea phase III clinical trial (BABY HUG): Challenges of study design

Bruce W. Thompson, Scott T. Miller, Zora R. Rogers, Renee C. Rees, Russell E. Ware, Myron A. Waclawiw, Rathi V. Iyer, James F. Casella, Lori Luchtman-Jones, Sohail Rana, Courtney D. Thornburg, Ram V. Kalpatthi, Julio Barredo, R. Clark Brown, Sharada Sarnaik, Thomas H. Howard, Lori Luck, Winfred C. Wang

Research output: Contribution to journalArticle

41 Citations (Scopus)

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).

Original languageEnglish
Pages (from-to)250-255
Number of pages6
JournalPediatric Blood and Cancer
Volume54
Issue number2
DOIs
StatePublished - Feb 1 2010

Fingerprint

Phase III Clinical Trials
Hydroxyurea
Pediatrics
Spleen
Research Subjects
Kidney
Sickle Cell Anemia
Sample Size
Placebos
Maintenance
Research Personnel
Clinical Trials
Safety
Brain
Pharmaceutical Preparations
Therapeutics

Keywords

  • Clinical trial
  • Hydroxyurea
  • Infants
  • Sickle cell

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Thompson, B. W., Miller, S. T., Rogers, Z. R., Rees, R. C., Ware, R. E., Waclawiw, M. A., ... Wang, W. C. (2010). The pediatric hydroxyurea phase III clinical trial (BABY HUG): Challenges of study design. Pediatric Blood and Cancer, 54(2), 250-255. https://doi.org/10.1002/pbc.22269

The pediatric hydroxyurea phase III clinical trial (BABY HUG) : Challenges of study design. / Thompson, Bruce W.; Miller, Scott T.; Rogers, Zora R.; Rees, Renee C.; Ware, Russell E.; Waclawiw, Myron A.; Iyer, Rathi V.; Casella, James F.; Luchtman-Jones, Lori; Rana, Sohail; Thornburg, Courtney D.; Kalpatthi, Ram V.; Barredo, Julio; Brown, R. Clark; Sarnaik, Sharada; Howard, Thomas H.; Luck, Lori; Wang, Winfred C.

In: Pediatric Blood and Cancer, Vol. 54, No. 2, 01.02.2010, p. 250-255.

Research output: Contribution to journalArticle

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, J, Brown, RC, Sarnaik, S, Howard, TH, Luck, L & Wang, WC 2010, 'The pediatric hydroxyurea phase III clinical trial (BABY HUG): Challenges of study design', Pediatric Blood and Cancer, vol. 54, no. 2, pp. 250-255. https://doi.org/10.1002/pbc.22269
Thompson BW, Miller ST, Rogers ZR, Rees RC, Ware RE, Waclawiw MA et al. The pediatric hydroxyurea phase III clinical trial (BABY HUG): Challenges of study design. Pediatric Blood and Cancer. 2010 Feb 1;54(2):250-255. https://doi.org/10.1002/pbc.22269
Thompson, Bruce W. ; Miller, Scott T. ; Rogers, Zora R. ; Rees, Renee C. ; Ware, Russell E. ; Waclawiw, Myron A. ; Iyer, Rathi V. ; Casella, James F. ; Luchtman-Jones, Lori ; Rana, Sohail ; Thornburg, Courtney D. ; Kalpatthi, Ram V. ; Barredo, Julio ; Brown, R. Clark ; Sarnaik, Sharada ; Howard, Thomas H. ; Luck, Lori ; Wang, Winfred C. / The pediatric hydroxyurea phase III clinical trial (BABY HUG) : Challenges of study design. In: Pediatric Blood and Cancer. 2010 ; Vol. 54, No. 2. pp. 250-255.
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