@article{de735ee8629141509e45d43d9fc73b61,
title = "Inhaled PGE1 in neonates with hypoxemic respiratory failure: Two pilot feasibility randomized clinical trials",
abstract = "Background: Inhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized the treatment of neonatal hypoxemic respiratory failure (NHRF). However, there is lack of sustained improvement in 30 to 46% of infants. Aerosolized prostaglandins I2 (PGI2) and E1 (PGE1) have been reported to be effective selective pulmonary vasodilators. The objective of this study was to evaluate the feasibility of a randomized controlled trial (RCT) of inhaled PGE1 (IPGE1) in NHRF. Methods: Two pilot multicenter phase II RCTs are included in this report. In the first pilot, late preterm and term neonates with NHRF, who had an oxygenation index (OI) of ≥15 and <25 on two arterial blood gases and had not previously received INO, were randomly assigned to receive two doses of IPGE1 (300 and 150 ng/kg/min) or placebo. The primary outcome was the enrollment of 50 infants in six to nine months at 10 sites. The first pilot was halted after four months for failure to enroll a single infant. The most common cause for non-enrollment was prior initiation of INO. In a re-designed second pilot, co-administration of IPGE1 and INO was permitted. Infants with suboptimal response to INO received either aerosolized saline or IPGE1 at a low (150 ng/kg/min) or high dose (300 ng/kg/min) for a maximum duration of 72 hours. The primary outcome was the recruitment of an adequate number of patients (n = 50) in a nine-month-period, with fewer than 20% protocol violations. Results: No infants were enrolled in the first pilot. Seven patients were enrolled in the second pilot; three in the control, two in the low-dose IPGE1, and two in the high-dose IPGE1 groups. The study was halted for recruitment futility after approximately six months as enrollment targets were not met. No serious adverse events, one minor protocol deviation and one pharmacy protocol violation were reported. Conclusions: These two pilot RCTs failed to recruit adequate eligible newborns with NHRF. Complex management RCTs of novel therapies for persistent pulmonary hypertension of the newborn (PPHN) may require novel study designs and a longer period of time from study approval to commencement of enrollment. Trial registration: ClinicalTrials.gov: Pilot one: NCT number: 00598429. registered on 10 January 2008. Last updated: 3 February 2013.",
keywords = "Aerosols, Clinical trial, Hypoxemic respiratory failure, Nebulizers, Neonatal, Prostaglandins, Pulmonary hypertension",
author = "{Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network} and Sood, {Beena G.} and Martin Keszler and Meena Garg and Klein, {Jonathan M.} and Robin Ohls and Namasivayam Ambalavanan and Cotten, {C. Michael} and Monica Malian and Sanchez, {Pablo J.} and Satyan Lakshminrusimha and Nelin, {Leif D.} and {Van Meurs}, {Krisa P.} and Rebecca Bara and Shampa Saha and Abhik Das and Dennis Wallace and Higgins, {Rosemary D.} and Seetha Shankaran and Besner, {Gail E.} and Patricia Luzader and Chicoine, {Louis G.} and Jenna Gabrio and {O'Donnell Auman}, Jeanette and Zaterka-Baxter, {Kristin M.} and Stevenson, {David K.} and {Bethany Ball}, M. and Steven Chinn and Proud, {Melinda S.} and Carlo, {Waldemar A.} and Collins, {Monica V.} and Cosby, {Shirley S.} and Zahra Davis and Quinn, {Rebecca J.} and Denson, {Brenda Reed} and Uday Devaskar and Teresa Chanlaw and Rachel Geller and Bell, {Edward F.} and Widness, {John A.} and Johnson, {Karen J.} and Campbell, {Donia B.} and Colaizy, {Tarah T.} and Dagle, {John M.} and Ellsbury, {Dan L.} and Johnson, {Kristine M.} and Lynn Messina and Nohr, {Joanna L.} and Watterberg, {Kristi L.} and Lacy, {Conra Backstrom} and Brian Walsh",
note = "Funding Information: The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Center for Research Resources, and the National Center for Advancing Translational Sciences provided grant support for the Neonatal Research Network{\textquoteright}s IPGE1 Studies through cooperative agreements. While NICHD staff did have input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of the NICHD. Data collected at participating sites of the NICHD Neonatal Research Network (NRN) were transmitted to RTI International, the data coordinating center (DCC) for the network, which stored, managed, and analyzed the data for this study. On behalf of the NRN, Drs Abhik Das (DCC Principal Investigator) and Shampa Saha (DCC Statistician) had full access to all of the data in the study, and with the NRN Center Principal Investigators, take responsibility for the integrity of the data and accuracy of the data analysis. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. The following investigators, in addition to those listed as authors, participated in this study: NRN Steering Committee Chairs: Division of Neonatology, College of Physicians and Surgeons, Columbia University: Richard A Polin, MD (2011 to present). Publisher Copyright: {\textcopyright} 2014 Sood et al.; licensee BioMed Central.",
year = "2014",
month = dec,
day = "12",
doi = "10.1186/1745-6215-15-486",
language = "English (US)",
volume = "15",
journal = "Trials",
issn = "1745-6215",
publisher = "BioMed Central",
number = "1",
}