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

J Perinatol. 2017 Nov;37(11):1220-1223. doi: 10.1038/jp.2017.131. Epub 2017 Sep 7.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cardiotonic Agents / therapeutic use*
  • Critical Illness / therapy
  • Double-Blind Method
  • Early Termination of Clinical Trials
  • Heart Defects, Congenital / drug therapy
  • Heart Failure / drug therapy*
  • Humans
  • Hydrocortisone / therapeutic use*
  • Infant, Newborn
  • Infant, Premature
  • Informed Consent
  • Neurodevelopmental Disorders / prevention & control
  • Patient Selection*

Substances

  • Cardiotonic Agents
  • Hydrocortisone