Inhaled PGE1 in Neonatal Hypoxemic Respiratory Failure (IPGE1)

Randomized Clinical Trial of Inhaled PGE1 (IPGE1) in Neonatal Hypoxemic Respiratory Failure. A Protocol for the NICHD Neonatal Research Network

This pilot study was a randomized, placebo-controlled, clinical trial to test the safety of using the intravenous form of Prostaglandin E1 (PGE1) in an inhaled form for treatment of hypoxemic respiratory failure in term newborns. The study planned to enroll 50 infants diagnosed with hypoxemic respiratory failure at nine NICHD Neonatal Research Network sites, and randomly assign them to receive one dose over a 72-hour period of either high concentration PGE1 (300 ng/kg/min), low concentration PGE1 (150 ng/kg/min), or placebo (normal saline, the diluent for the drug). In addition to determining the safety, optimal dose, and duration of the therapy, this pilot trial planned to evaluate the feasibility of conducting a larger, multi-center randomized, blinded placebo-controlled trial.

Study Overview

• Status: Withdrawn
• Conditions: Streptococcal Infections; Respiratory Insufficiency; Pulmonary Hypertension; Respiratory Distress Syndrome, Newborn; Infant, Newborn
• Intervention / Treatment: Drug: Inhaled Prostaglandin E1

Detailed Description

Hypoxemic respiratory failure (HRF), frequently associated with persistent pulmonary hypertension of the newborn (PPHN), is a rare, but life-threatening condition affecting approximately 2 to 9 percent of infants admitted to neonatal intensive care units and results in significant morbidity and mortality. It occurs more often in full- or post-term babies whose circulatory systems do not adapt well to breathing outside the womb. HRF may result from congenital hernia of the diaphragm, group B streptococcal infection, inhaling meconium in the womb, or respiratory distress syndrome.

Medical treatments, such as high frequency ventilation, inhaled nitric oxide, and Extracorporeal Membrane Oxygenation (ECMO, a heart and lung support machine), have significantly increased survival of children with HRF. These therapies, while successful, however, have a variety of side effects and potential long-term disabilities.

This feasibility trial was designed to test the safety of using the intravenous form of Prostaglandin E1 in an inhaled form (iPGE1) on infants born at 34 0/7ths weeks gestational age or greater diagnosed with hypoxemic respiratory failure and on assisted ventilation. The intravenous form of PGE1 was to be aerosolized and administered via a nebulizer attached to the infant's ventilator. The goal was to enroll 50 subjects within 6-9 months, in preparation for a larger, multi-center randomized control trial; however, the study was withdrawn for lack of recruitment.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Durham, North Carolina, United States, 27705
      • RTI International
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University, Rainbow Babies and Children's Hospital
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center at Dallas
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 week (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants born at 34 0/7ths weeks gestational age or greater (by best obstetrical estimate) and at a postnatal age no greater than 7 days (168 hours)
• Infants diagnosed with hypoxemic respiratory failure (HRF), including perinatal aspiration syndrome (meconium, blood, or amniotic fluid), pneumonia/ sepsis, respiratory distress syndrome, or idiopathic respiratory failure
• Infants who will receive assisted ventilation for HRF
• Infants with an oxygenation index (MAP x FiO2 x 100/PaO2)(OI) of 15-25 on two arterial gases taken between 15 minutes and 12 hours apart
• An indwelling arterial line
• Infants whose parents/legal guardians have provided consent for enrollment

Exclusion Criteria:

• Any infant in whom a decision has been made not to provide full treatment
• Known structural congenital heart disease, except patent ductus arteriosus and atrial/ventricular level shunts
• Congenital diaphragmatic hernia
• Preterm neonates less than 34 weeks
• Thrombocytopenia (platelet count < 80,000/μl) unresponsive to platelet transfusion
• Infants receiving hypothermia for hypoxic ischemic encephalopathy
• Previous treatment with inhaled nitric oxide
• Infants already enrolled in a conflicting and/or Investigational New Drug (IND) clinical trial
• Infants whose parents/legal guardians refuse consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High dose; PGE1 300 ng/kg/min via nebulizer over a 72-hour period	Drug: Inhaled Prostaglandin E1; Delivery of one dose of either high dose PGE1 (300 ng/kg/min), low dose PGE1 (150 ng/kg/min), or placebo (normal saline, the diluent for the drug) via nebulizer over a 72-hour period; Other Names: Alprostadil
Active Comparator: Low dose; PGE1 150 ng/kg/min via nebulizer over a 72-hour period	Drug: Inhaled Prostaglandin E1; Delivery of one dose of either high dose PGE1 (300 ng/kg/min), low dose PGE1 (150 ng/kg/min), or placebo (normal saline, the diluent for the drug) via nebulizer over a 72-hour period; Other Names: Alprostadil
Placebo Comparator: Placebo; Normal saline, the diluent for the drug, via nebulizer over a 72-hour period	Drug: Inhaled Prostaglandin E1; Delivery of one dose of either high dose PGE1 (300 ng/kg/min), low dose PGE1 (150 ng/kg/min), or placebo (normal saline, the diluent for the drug) via nebulizer over a 72-hour period; Other Names: Alprostadil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The ability to recruit an adequate number of patients (n = 50) in a 6-9 month period without excessive (>20%) protocol violations.	6-9 months after trial begins recruitment

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of mechanical ventilation
Length of hospitalization
Progression to an OI greater than 25	72-hours after enrollment
Improvement in partial pressure of oxygen (PaO2) in the blood gas	72-hours after enrollment
Change in OI	72 hours after enrollment
Death	72-hours after intervention
Need for inhaled nitric oxide or ECMO	72-hours after enrollment
Number of days of oxygen used and need for supplemental oxygen at 28 days of life
Occurrence of grade III-IV intracranial hemorrhage and cystic leukomalacia

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications and helpful links

General Publications

• Sood BG, Keszler M, Garg M, Klein JM, Ohls R, Ambalavanan N, Cotten CM, Malian M, Sanchez PJ, Lakshminrusimha S, Nelin LD, Van Meurs KP, Bara R, Saha S, Das A, Wallace D, Higgins RD, Shankaran S; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Inhaled PGE1 in neonates with hypoxemic respiratory failure: two pilot feasibility randomized clinical trials. Trials. 2014 Dec 12;15:486. doi: 10.1186/1745-6215-15-486.

Helpful Links

• NICHD Neonatal Research Network

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: January 10, 2008
• First Submitted That Met QC Criteria: January 10, 2008
• First Posted (Estimate): January 21, 2008

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Mechanical ventilation; NICHD Neonatal Research Network; Hypoxemic respiratory failure (HRF); Persistent pulmonary hypertension of the newborn (PPHN); Prostaglandin E1 (PGE1); Meconium, aspiration
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infant, Premature, Diseases; Hypertension; Respiratory Insufficiency; Hypertension, Pulmonary; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Streptococcal Infections; Vasodilator Agents; Urological Agents; Platelet Aggregation Inhibitors; Alprostadil
• Other Study ID Numbers: NICHD-NRN-0037; U10HD036790 (U.S. NIH Grant/Contract); U10HD021364 (U.S. NIH Grant/Contract); U10HD021385 (U.S. NIH Grant/Contract); U10HD027880 (U.S. NIH Grant/Contract); U10HD034216 (U.S. NIH Grant/Contract); U10HD040492 (U.S. NIH Grant/Contract); U10HD040689 (U.S. NIH Grant/Contract); U10HD053089 (U.S. NIH Grant/Contract); U10HD053109 (U.S. NIH Grant/Contract); U10HD053119 (U.S. NIH Grant/Contract); U10HD053124 (U.S. NIH Grant/Contract)