Inhaled Prostaglandin E1 (IPGE1) for Hypoxemic Respiratory Failure (NHRF)



Status:Terminated
Conditions:High Blood Pressure (Hypertension), Cardiology, Hospital, Pulmonary
Therapuetic Areas:Cardiology / Vascular Diseases, Pulmonary / Respiratory Diseases, Other
Healthy:No
Age Range:Any
Updated:3/30/2019
Start Date:November 2011
End Date:June 2012

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Pilot Randomized Clinical Trial of Inhaled PGE1 in Neonates With Sub-Optimal Response to Inhaled Nitric Oxide

This is a randomized controlled trial (RCT) on the use of Inhaled prostaglandin E1 (IPGE1) in
Neonatal Hypoxemic Respiratory Failure (NHRF). Fifty patients recruited at 10 high volume
sites within the NICHD Neonatal Research Network will constitute a pilot sample to evaluate
the feasibility and safety of prolonged IPGE1 administration and determination of optimal
dose. In this Pilot RCT, two doses of IPGE1 (300 and 150 ng/kg/min) will be administered over
a maximum duration of 72 hours and compared with placebo. Once feasibility and safety of
IPGE1 administered over 72 hours has been demonstrated in the pilot trial, a full scale
randomized controlled trial will be planned.

Hypoxemic respiratory failure in the newborn (NHRF) is usually associated with widespread
vasoconstriction of the pulmonary microvasculature giving rise to intra- and extra-pulmonary
shunts and profound hypoxemia. The goal of therapy is to decrease the regional pulmonary
vascular resistance of ventilated lung areas thus decreasing intrapulmonary shunting and
selectively reducing the pulmonary-artery pressure without causing systemic vasodilation.
Intravenously administered vasodilators lack pulmonary selectivity leading to systemic side
effects. Inhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized
the treatment of respiratory failure in the newborn. However, there is lack of sustained
improvement in 30-46% of infants; moreover, INO requires specialized systems for
administration, making the treatment expensive. Aerosolized prostaglandins I2 and E1 have
been reported to be effective selective pulmonary vasodilators in animals and human adults.
In addition, inhaled prostaglandin I2 (IPGI2) has also been reported to be effective in
preterm and term newborns, and children with pulmonary hypertension. Although intravenous
PGE1 is widely used in neonates, the use of the inhaled form has not been reported in
newborns with pulmonary hypertension. Compared to PGI2, PGE1 has a shorter half-life, lower
acidity constant (pKa) (6.3 versus 10.5), bronchodilator action, anti-proliferative and
anti-inflammatory effects on the alveolar, interstitial and vascular spaces of the lung.
Prostaglandin nebulization can be used without the sophisticated technical equipment needed
for controlled NO inhalation and hence is less expensive. It has no known toxic metabolites
or toxic effects. Prostaglandins and nitric oxide (NO) relax the vascular smooth muscles
through two different second-messenger systems; therefore, in combination, INO and IPGE1 may
have synergistic effect. The existing literature suggests that inhaled PGE1 is a potential
effective vasodilator in the treatment of NHRF . We have reported the safety and feasibility
of short-term administration of inhaled PGE1 in an un-blinded Phase I/II dose-escalation
study. Four doses ranging from 25 to 300 ng/kg/min were tested for a maximum duration of 3
hours. We have also reported the stability of IPGE1, its emitted dose and aerosol particle
size distribution (APSD) in a neonatal ventilator circuit. In addition we have demonstrated
the safety of high dose IPGE1 (1200 ng/kg/min) over 24 hours in ventilated piglets. In the
current protocol, we propose a pilot to evaluate the feasibility and safety of prolonged
IPGE1 in NHRF. Two doses of IPGE1 (300 and 150 ng/kg/min) will be tested followed by weaning
for a maximum duration of 72 hours to determine feasibility, safety, optimal dose and
duration of therapy in 50 patients in ten NICHD NRN sites. An IND status has been approved by
the FDA for this trial.

Inclusion Criteria:

- Gestational age less than or equal to 34 weeks

- Postnatal age less than or equal to 7 days (168 hours).

- Assisted ventilation for hypoxemic respiratory failure.

- Diagnosis of NHRF including perinatal aspiration syndrome (meconium, blood, or
amniotic fluid), suspected/proven pneumonia/sepsis, respiratory distress syndrome,
idiopathic persistent pulmonary hypertension of the newborn (PPHN) or suspected
pulmonary hypoplasia.

- Receiving INO for at least 1 hour and not >72 hours.

- Oxygenation Index (OI ) ≥ 15 on any 2 arterial blood gases 15 minutes to 12 hours
apart while on INO.

- An indwelling arterial line is present

Exclusion Criteria:

- Any infant in whom a decision has been made not to provide full treatment (e.g.
chromosomal anomalies, severe birth asphyxia).

- Known structural congenital heart disease except patent ductus arteriosus and
atrial/ventricular level shunts.

- Congenital diaphragmatic hernia.

- Thrombocytopenia unresponsive to platelet transfusion.

- Enrollment in a conflicting and/or Investigational New Drug (IND) clinical trial.
We found this trial at
11
sites
60 Crittenden Blvd # 70
Rochester, New York 14642
(585) 275-2121
University of Rochester The University of Rochester is one of the country's top-tier research universities....
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Rochester, NY
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1720 2nd Ave S
Birmingham, Alabama 35233
(205) 934-4011 
University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
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Birmingham, AL
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5323 Harry Hines Blvd
Dallas, Texas 75235
(214) 648-3111
Univ of Texas, Southwestern Med Ctr of Dallas The story of UT Southwestern Medical Center...
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Dallas, TX
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5050 Anthony Wayne Dr
Detroit, Michigan 48201
(313) 577-2424
Wayne State University Founded in 1868, Wayne State University is a nationally recognized metropolitan research...
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Detroit, MI
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Durham, North Carolina 27710
(919) 684-8111
Duke University Younger than most other prestigious U.S. research universities, Duke University consistently ranks among...
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Durham, NC
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101 Jessup Hall
Iowa City, Iowa 52242
(319) 335-3500
University of Iowa With just over 30,000 students, the University of Iowa is one of...
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Iowa City, IA
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Los Angeles, California 90095
310-825-4321
University of California at Los Angeles The University of California, Los Angeles (UCLA) is an...
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Los Angeles, CA
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Providence, RI
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Albuquerque, New Mexico 87131
(505) 277-0111
University of New Mexico Founded in 1889 as New Mexico’s flagship institution, the University of...
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Albuquerque, NM
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Columbus, OH
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Palo Alto, California 94304
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Palo Alto, CA
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