Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants

Abhik Das; Benjamin Alan Carper; Kristi L. Watterberg; E Fernandez; Michele C. Walsh; William E Truog; Barbara J Stoll; G M Sokol; Kathleen A Kennedy; M V Fraga; S S Beauman; Benjamin Alan Carper; Abhik Das; Andrea F Duncan; W F Buss; C Gauldin; C B Lacy; Pablo J. Sanchez; Sanjay Chawla; S Lakshminrusimha; C. Michael Cotten; Krisa P. Van Meurs; B Poindexter; E. F. Bell; Waldemar A Carlo; U Devaskar; Myra H Wyckoff; Rosemary D. Higgins

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants

Watterberg, K. L., Fernandez, E., Walsh, M. C., Truog, W. E., Stoll, B. J., Sokol, G. M., Kennedy, K. A., Fraga, M. V., Beauman, S. S., Carper, B., Das, A., Duncan, A. F., Buss, W. F., Gauldin, C., Lacy, C. B., Sanchez, P. J., Chawla, S., Lakshminrusimha, S., Cotten, C. M., ... Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (2017). Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants. Journal of Perinatology, 37(11), 1220-1223. https://doi.org/10.1038/jp.2017.131

Copy citation

Abstract

OBJECTIVE: To analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.

STUDY DESIGN: The original study was a multicenter RCT. Eligibility: >= 34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.

RESULTS: Two hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.

CONCLUSION: Despite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives.