Professor Nationwide Children's Hospital The Ohio State University Columbus, Ohio, United States
Background: This observational registry evaluated iNO use in PT vs TNT neonates with hypoxicrespiratory failure (HRF) associated with PH (PaTTerN; NCT03132428).
Design/Methods: Data were retrospectively collected from neonates of gestational age ≥27–<34 weeks (PT) or ≥34–≤40 weeks (TNT) with confirmed PH, received iNO for ≥24–96 hours as part of routine clinical practice, and were 0–7 days old at initiation of iNO. HRF severity was measured by oxygenation index (OI) for mechanically ventilated neonates or surrogate OI (SOI; defined as CPAP x FiO2 x 100/PaO2 for neonates on CPAP or PEEP x FiO2 x 100/PaO2 for those on noninvasive mechanical ventilation). Outcomes included PT vs TNT neonates achieving ≥25% decrease in OI/SOI (ie, response) during iNO treatment vs baseline (primary endpoint); ≥25% decrease in OI/SOI by severity (mild, OI <16 or SOI <10; moderate, OI 16–25 or SOI 10–15; severe, OI >25 or SOI >15 or progression to mechanical ventilation); time to ≥25% decrease in OI/SOI overall and by severity; effect of demographic parameters on OI/SOI; and partial or nonresponders (<25% decrease in OI/SOI).
Results: 140 neonates (PT, n=55; TNT, n=85) were enrolled; 51% completed 96 hours of treatment (mean [SD] 7.0 [6.2] days). Mean (SD) birth weight was 1324 (481) g in PT and 3312 (797) g in TNT neonates. Median (min, max) Apgar scores at 1 minute were lower (3.0 [1, 8] vs 7.0 [1, 9) in PT vs TNT neonates. A ≥25% decrease in OI/SOI was achieved in 50 (90.9%) PT vs 75 (88.2%) TNT neonates (difference [95% CI]: 0.0267 [-0.0333, 0.0868]). Efficacy in the PT group was noninferior to the TNT group, as the lower bound of the CI was greater than the predefined margin (-0.1452). Proportions of neonates with ≥25% OI/SOI decrease were similar across severity groups, with no significant between-group difference in time to improvement (Table). Univariate analysis showed that white race neonates were 69% more likely than nonwhite neonates to achieve a ≥25% decrease in OI/SOI (white vs nonwhite, odds ratio [95% CI], 1.69 [1.2, 2.4]; P=0.0026). More TNT neonates than PT had no response (<5% response) to iNO (9 [10.6%] vs 3 [5.5%]). No treatment-related adverse events of special interest were reported. Conclusion(s): These data suggest that use of iNO in routine clinical practice for improving oxygenation in PT neonates with PH associated with HRF is at least as effective as in TNT neonates. Funded by Mallinckrodt Pharmaceuticals.
Summary of Key Efficacy Endpoints in Preterm and Term/Near-Term Neonates With Pulmonary Hypertension Receiving Inhaled Nitric Oxide by Hypoxic Respiratory Failure Severity
Authors/Institutions: Leif D. Nelin, The Research Institute at Nationwide Children’s Hospital, Ohio State University, Columbus, Ohio, United States; John P. Kinsella, University of Colorado School of Medicine/Children’s Hospital Colorado, Aurora, Colorado, United States; Sherry Courtney, Arkansas Children’s Hospital Research Institute, University of Arkansas for Medical Sciences/Arkansas Children’s Hospital, Little Rock, Arkansas, United States; Eugenia K. Pallotto, Children’s Mercy Hospital, Kansas City, Missouri, United States; Eva Tarau, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey, United States; Jim L. Potenziano, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey, United States