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Trials. 2014 Dec 12;15:486. doi: 10.1186/1745-6215-15-486.

Inhaled PGE1 in neonates with hypoxemic respiratory failure: two pilot feasibility randomized clinical trials.

Author information

1
Department of Pediatrics, Children's Hospital of Michigan, 3901 Beaubien Blvd., 4H42, Detroit, MI, 48201, USA. bsood@med.wayne.edu.
2
Department of Pediatrics, Women and Infants Hospital, Brown University, 101 Dudley Street, Providence, RI, 0290, USA. mkeszler@wihri.org.
3
Department of Pediatrics, University of California, 10833 Le Conte Avenue, Room B2-375 MDCC, Los Angeles, CA, 90095, USA. MGarg@mednet.ucla.edu.
4
Department of Pediatrics, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA. jonathan-klein@uiowa.edu.
5
MSC10 5590 1, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131-0001, USA. ROhls@salud.unm.edu.
6
Division of Neonatology, University of Alabama at Birmingham, 176F Suite 9380 619 South 19th St, Birmingham, AL, 35249-7335, UK. nambalavanan@peds.uab.edu.
7
Department of Pediatrics, Duke University, 2424 Erwin Road Suite 504, Durham, NC, 27705, USA. cotte010@mc.duke.edu.
8
Department of Pediatrics, Children's Hospital of Michigan, 3901 Beaubien Blvd., 4H42, Detroit, MI, 48201, USA. mmalian@dmc.org.
9
Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA. pablo.sanchez@nationwidechildrens.org.
10
Department of Pediatrics, University of Buffalo, 219 Bryant Street, Buffalo, NY, 14222, USA. slakshmi@buffalo.edu.
11
Department of Pediatrics, The Ohio State University and Nationwide Children's Hospital, 700 Children's Drive, W203, Columbus, OH, 43205, USA. Leif.Nelin@nationwidechildrens.org.
12
Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, 750 Welch Road, Suite 315, Palo Alto, CA, 94304, USA. vanmeurs@stanford.edu.
13
Department of Pediatrics, Children's Hospital of Michigan, 3901 Beaubien Blvd., 4H42, Detroit, MI, 48201, USA. bara@med.wayne.edu.
14
Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, NC, USA. saha@rti.org.
15
Social, Statistical and Environmental Sciences Unit, RTI International, 6110 Executive Blvd., Suite 902, Rockville, MD, 20852-3903, USA. adas@rti.org.
16
Social, Statistical and Environmental Sciences Unit, RTI International, 6110 Executive Blvd., Suite 902, Rockville, MD, 20852-3903, USA. dwallace@rti.org.
17
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rm 4B03, 6100 Executive Blvd., MSC 7510, Bethesda, MD, 20892-7510, USA. higginsr@mail.nih.gov.
18
Department of Pediatrics, Children's Hospital of Michigan, 3901 Beaubien Blvd., 4H42, Detroit, MI, 48201, USA. sshankar@med.wayne.edu.

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 2011. Pilot two: NCT number: 01467076 17 October 2011. Last updated: 13 February 2013.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00598429 NCT01467076.

PMID:
25496504
PMCID:
PMC4414424
DOI:
10.1186/1745-6215-15-486
[Indexed for MEDLINE]
Free PMC Article

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