Inhaled PGE1 in Neonatal Hypoxemic Respiratory Failure (IPGE1)

This study has been withdrawn prior to enrollment.
(Withdrawn due to lack of recruitment)
Sponsor:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00598429
First received: January 10, 2008
Last updated: February 13, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Infant, Newborn
Respiratory Insufficiency
Pulmonary Hypertension
Respiratory Distress Syndrome, Newborn
Streptococcal Infections
Drug: Inhaled Prostaglandin E1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial of Inhaled PGE1 (IPGE1) in Neonatal Hypoxemic Respiratory Failure. A Protocol for the NICHD Neonatal Research Network

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • The ability to recruit an adequate number of patients (n = 50) in a 6-9 month period without excessive (>20%) protocol violations. [ Time Frame: 6-9 months after trial begins recruitment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression to an OI greater than 25 [ Time Frame: 72-hours after enrollment ] [ Designated as safety issue: No ]
  • Improvement in partial pressure of oxygen (PaO2) in the blood gas [ Time Frame: 72-hours after enrollment ] [ Designated as safety issue: No ]
  • Change in OI [ Time Frame: 72 hours after enrollment ] [ Designated as safety issue: Yes ]
  • Death [ Time Frame: 72-hours after intervention ] [ Designated as safety issue: Yes ]
  • Need for inhaled nitric oxide or ECMO [ Time Frame: 72-hours after enrollment ] [ Designated as safety issue: Yes ]
  • Length of hospitalization [ Time Frame: TBD ] [ Designated as safety issue: No ]
  • Duration of mechanical ventilation [ Time Frame: TBD ] [ Designated as safety issue: Yes ]
  • Number of days of oxygen used and need for supplemental oxygen at 28 days of life [ Time Frame: TBD ] [ Designated as safety issue: Yes ]
  • Occurrence of grade III-IV intracranial hemorrhage and cystic leukomalacia [ Time Frame: TBD ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: May 2008
Estimated Study Completion Date: September 2008
Estimated Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Alprostadil

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.

  Eligibility

Ages Eligible for Study:   up to 7 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00598429

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
RTI International
Durham, North Carolina, United States, 27705
United States, Ohio
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84108
Sponsors and Collaborators
Investigators
Principal Investigator: Michele C. Walsh, MD MS Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: Ronald N. Goldberg, MD Duke University
Principal Investigator: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Ivan D. Frantz III, MD Tufts Medical Center
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Edward F. Bell, MD University of Iowa
Principal Investigator: Kristi L. Watterberg, MD University of New Mexico
Principal Investigator: Roger G. Faix, MD University of Utah
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Pablo J. Sanchez, MD University of Texas Southwestern Medical Center at Dallas
  More Information

Additional Information:
No publications provided

Responsible Party: Beena Sood, Lead Principal Investigator, Wayne State University, NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT00598429     History of Changes
Other Study ID Numbers: NICHD-NRN-0037, U10HD036790, U10HD021364, U10HD021385, U10HD027880, U10HD034216, U10HD040492, U10HD040689, U10HD053089, U10HD053109, U10HD053119, U10HD053124
Study First Received: January 10, 2008
Last Updated: February 13, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Hypoxemic respiratory failure (HRF)
Persistent pulmonary hypertension of the newborn (PPHN)
Prostaglandin E1 (PGE1)
Mechanical ventilation
Meconium, aspiration

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Respiratory Insufficiency
Streptococcal Infections
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Gram-Positive Bacterial Infections
Bacterial Infections
Alprostadil
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014