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

David Ley, Boubou Hallberg, Ingrid Hansen-Pupp, 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 MangiliJou-Ku Chung, Mark A. Turner, Lois E. H. Smith, Ann Hellström

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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.
Original languageEnglish
Pages (from-to)56-65.e8
JournalJournal of Pediatrics
Volume206
Early online date2018
DOIs
Publication statusPublished - Mar 2019

Cite this

Ley, D., Hallberg, B., Hansen-Pupp, I., Dani, C., Ramenghi, L. A., Marlow, N., ... Hellström, A. (2019). rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial. Journal of Pediatrics, 206, 56-65.e8. https://doi.org/10.1016/j.jpeds.2018.10.033