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- Ward, Robert M., et al.
(author)
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Development of the PREMature Infant Index (PREMII™), a clinician-reported outcome measure assessing functional status of extremely preterm infants
- 2022
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In: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 35:5, s. 941-950
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Journal article (peer-reviewed)abstract
- Background: Comprehensive measures to evaluate the effectiveness of medical interventions in extremely preterm infants are lacking. Although length of stay is used as an indicator of overall health among preterm infants in clinical studies, it is confounded by nonmedical factors (e.g. parental readiness and availability of home nursing support). Objectives: To develop the PREMature Infant Index (PREMII™), an electronic content-valid clinician-reported outcome measure for assessing functional status of extremely preterm infants (<28 weeks gestational age) serially over time in the neonatal intensive care unit. We report the development stages of the PREMII, including suggestions for scoring. Methods: We developed the PREMII according to US Food and Drug Administration regulatory standards. Development included five stages: (1) literature review, (2) clinical expert interviews, (3) Delphi panel survey, (4) development of items/levels, and (5) cognitive interviews/usability testing. Scoring approaches were explored via an online clinician survey. Results: Key factors reflective of functional status were identified by physicians and nurses during development of the PREMII, as were levels within each factor to assess functional status. The resulting PREMII evaluates eight infant health factors: respiratory support, oxygen administration, apnea, bradycardia, desaturation, thermoregulation, feeding, and weight gain, each scored with three to six gradations. Factor levels are standardized on a 0–100 scale; resultant scores are 0–100. No usability issues were identified. The online clinician survey identified optimal scoring methods to capture functional status at a given time point. Conclusions: Our findings support the content validity and usability of the PREMII as a multifunction outcome measure to assess functional status over time in extremely preterm infants. Psychometric validation is ongoing.
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- Chung, Jou Ku, et al.
(author)
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Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants
- 2017
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 81:3, s. 504-510
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Journal article (peer-reviewed)abstract
- Background:rhIGF-1/rhIGFBP-3 is being investigated for prevention of retinopathy of prematurity in extremely preterm infants.Methods:A population pharmacokinetic model was developed using data from phase I/II (Sections A-C) trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict optimal dosing to establish/maintain serum IGF-1 within physiological intrauterine levels. In Section D of the phase II study, infants (gestational age (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at the model-predicted dose of 250 μg/kg/d continuous i.v. infusion up to postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic analysis was performed for the first 10 treated infants to verify dosing.Results:Serum IGF-1 data were reviewed for 10 treated/9 control infants. Duration of therapy in treated infants ranged 1-34.5 d. At baseline (before infusion and <24 h from birth), mean (SD) IGF-1 was 19.2 (8.0) μg/l (treated) and 15.4 (4.7) μg/l (controls). Mean (SD) IGF-1 increased to 45.9 (19.6) μg/l at 12 h in treated infants, and remained within target levels for all subsequent timepoints. For treated infants, 88.8% of the IGF-1 measurements were within target levels (controls, 11.1%).Conclusion:Through the reported work, we determined appropriate rhIGF-1/rhIGFBP-3 dosing to achieve physiological intrauterine serum IGF-1 levels in extremely preterm infants.
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- Hansen-Pupp, Ingrid, et al.
(author)
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Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study
- 2017
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In: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374. ; 36, s. 44-51
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Journal article (peer-reviewed)abstract
- Objective To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (< 28 weeks' gestational age), based on initial sections of a phase II randomized controlled trial. Design The phase II trial was designed in four sections (A–D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C. Infants in these study sections received rhIGF-1/rhIGFBP-3 or standard neonatal care up to postmenstrual age (weeks + days) 28 + 6 (Section B) or 29 + 6 (Section C). Dosing was variable/individualized and intended to establish serum IGF-1 within physiological intrauterine levels. Results Nineteen infants were enrolled across Sections B/C: nine received rhIGF-1/rhIGFBP-3 and 10 standard neonatal care. Among the nine infants treated with study drug, mean (SD) dose was 95.1 (10.6) μg/kg/day and mean (SD) duration of infusion was 14.2 (6.1) days. Eight of nine (88.9%) treated infants had two or more dose changes during treatment. Mean serum IGF-1 levels during treatment were 23 μg/L among treated infants compared with 14 μg/L in control infants. Overall, 66.3% of IGF-1 measurements for treated infants were within target levels (20–60 μg/L) versus 17.3% for control infants. Overall incidence of adverse events (AEs) was similar for treated versus control infants; AEs were generally as expected in this population, and no AEs were considered related to study treatment. There was no observed increase in infection rates (considered a possible risk with continuous intravenous infusion) between treated and control infants. Rates of hypoglycemia (considered a possible risk with IGF-1 treatment) were also similar between groups. There was one fatal serious AE of cardiac tamponade in the treated group (not considered treatment related). Conclusion Infusion of rhIGF-1/rhIGFBP-3 increased serum concentrations of IGF-1 and attainment of target levels relative to standard neonatal care. rhIGF-1/rhIGFBP-3 infusion was well tolerated with no safety signals. Although further work is required to optimize the dose regimen for attainment of physiological intrauterine levels, we believe the results reported support the feasibility of rhIGF-1/rhIGFBP-3 continuous longitudinal infusion in extremely preterm infants. The trial is registered at ClinicalTrials.gov (NCT01096784). © 2017 The Authors
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