rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial

Research output: Contribution to journalArticle

Abstract

Objective: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. Study design: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. Results: Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. Conclusions: rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. Trial registration: ClinicalTrials.gov: NCT01096784.

Details

Authors
  • Boubou Hallberg
  • Carlo Dani
  • Luca A. Ramenghi
  • Neil Marlow
  • Kathryn Beardsall
  • Faizah Bhatti
  • David Dunger
  • Jason D. Higginson
  • Ajit Mahaveer
  • Olachi J. Mezu-Ndubuisi
  • Peter Reynolds
  • Carmen Giannantonio
  • Mirjam van Weissenbruch
  • Norman Barton
  • Adina Tocoian
  • Mohamed Hamdani
  • Emily Jochim
  • Alexandra Mangili
  • Jou Ku Chung
  • Mark A. Turner
  • Lois E.H. Smith
  • Ann Hellström
Organisations
External organisations
  • Karolinska University Hospital
  • Careggi University Hospital
  • Gaslini Children's Hospital
  • University College London
  • University of Cambridge
  • University of Wisconsin-Madison
  • Policlinico Universitario Agostino Gemelli
  • Amsterdam UMC - Vrije Universiteit Amsterdam
  • University of Liverpool
  • Boston Children's Hospital
  • University of Gothenburg
  • Skåne University Hospital
  • Karolinska Institutet
  • University of Florence
  • University of Oklahoma Health Sciences Center
  • East Carolina University
  • St. Mary’s Hospital, Manchester
  • University of Manchester
  • St Peter's Hospital, Chertsey
  • Shire
  • Shire Switzerland GmbH
  • Harvard University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pediatrics

Keywords

  • bronchopulmonary dysplasia, intraventricular hemorrhage, neonatology, retinopathy of prematurity
Original languageEnglish
Pages (from-to)56-65.e8
JournalJournal of Pediatrics
Volume206
Early online date2018 Nov 22
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes