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

Ley, David LU ; Hallberg, Boubou; Hansen-Pupp, Ingrid LU ; Dani, Carlo; Ramenghi, Luca A.; Marlow, Neil; Beardsall, Kathryn; Bhatti, Faizah; Dunger, David and Higginson, Jason D., et al. (2019) In Journal of Pediatrics 206. p.8-65
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... (More)

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.

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published
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keywords
bronchopulmonary dysplasia, intraventricular hemorrhage, neonatology, retinopathy of prematurity
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Journal of Pediatrics
volume
206
pages
8 - 65
publisher
Academic Press
external identifiers
  • scopus:85056881379
ISSN
0022-3476
DOI
10.1016/j.jpeds.2018.10.033
language
English
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yes
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553ccf70-2df4-4119-b911-cebd09336a8c
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2018-11-30 09:34:38
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2019-07-16 04:01:28
@article{553ccf70-2df4-4119-b911-cebd09336a8c,
  abstract     = {<p>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 23<sup>0/7</sup> weeks to 27<sup>6/7</sup> weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from &lt;24 hours of birth to postmenstrual age 29<sup>6/7</sup> weeks) or standard neonatal care, with follow-up to a postmenstrual age of 40<sup>4/7</sup> 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.</p>},
  author       = {Ley, David and Hallberg, Boubou and Hansen-Pupp, Ingrid and Dani, Carlo and Ramenghi, Luca A. and Marlow, Neil and Beardsall, Kathryn and Bhatti, Faizah and Dunger, David and Higginson, Jason D. and Mahaveer, Ajit and Mezu-Ndubuisi, Olachi J. and Reynolds, Peter and Giannantonio, Carmen and van Weissenbruch, Mirjam and Barton, Norman and Tocoian, Adina and Hamdani, Mohamed and Jochim, Emily and Mangili, Alexandra and Chung, Jou Ku and Turner, Mark A. and Smith, Lois E.H. and Hellström, Ann},
  issn         = {0022-3476},
  keyword      = {bronchopulmonary dysplasia,intraventricular hemorrhage,neonatology,retinopathy of prematurity},
  language     = {eng},
  pages        = {8--65},
  publisher    = {Academic Press},
  series       = {Journal of Pediatrics},
  title        = {rhIGF-1/rhIGFBP-3 in Preterm Infants : A Phase 2 Randomized Controlled Trial},
  url          = {http://dx.doi.org/10.1016/j.jpeds.2018.10.033},
  volume       = {206},
  year         = {2019},
}