Inhaled PGE1 in Neonatal Hypoxemic Respiratory Failure - Full Text View

Sponsored by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00598429

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 II

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure Pulmonary Hypertension Streptococcal Infections

Drug Information available for: Sodium chloride Alprostadil

U.S. FDA Resources

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

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
Study Completion Date:	September 2008
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
High dose: Active Comparator 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
Low dose: Active Comparator 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
Placebo: Placebo Comparator 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

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 terminated 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
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

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:	Michele C. Walsh, MD MS	Case Western Reserve University
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

NICHD Neonatal Research Network This link exits the ClinicalTrials.gov site

Responsible Party:	Wayne State University, NICHD Neonatal Research Network ( Beena Sood, Lead Principal Investigator )
Study ID Numbers:	NICHD-NRN-0035, CCTS UL1 RR24128 (Duke), CCTS UL1 RR24979 (Iowa), CCTS UL1 RR24982 (Dallas), CCTS UL1 RR24989 (Case), CCTS UL1 RR25744 (Stanford), CCTS UL1 RR25752 (Tufts), CCTS UL1 RR25764 (Utah), CCTS UL1 RR25777 (Alabama), GCRC M01 RR30 (Duke), GCRC M01 RR32 (Alabama), GCRC M01 RR54 (Tufts), GCRC M01 RR59 (Iowa), GCRC M01 RR633 (Dallas), GCRC M01 RR64 (Utah), GCRC M01 RR70 (Stanford), GCRC M01 RR80 (Case), U01 HD36790 (RTI), U10 HD21364 (Case), U10 HD21385 (Wayne), U10 HD27880 (Stanford), U10 HD34216 (Alabama), U10 HD40492 (Duke), U10 HD40689 (Dallas), U10 HD53089 (New Mexico), U10 HD53109 (Iowa), U10 HD53119 (Tufts), U10 HD53124 (Utah)
Study First Received:	January 10, 2008
Last Updated:	December 4, 2008
ClinicalTrials.gov Identifier:	NCT00598429
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

Study placed in the following topic categories:

Alprostadil
Bacterial Infections
Respiratory Distress Syndrome, Adult
Respiration Disorders
Respiratory Distress Syndrome, Newborn
Vascular Diseases
Infant, Premature, Diseases
Gram-Positive Bacterial Infections
Respiratory Insufficiency

Respiratory Tract Diseases
Streptococcal Infections
Hypertension, Pulmonary
Lung Diseases
Persistent Fetal Circulation Syndrome
Infant, Newborn, Diseases
Acute respiratory distress syndrome
Hypertension

Additional relevant MeSH terms:

Vasodilator Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Hematologic Agents
Platelet Aggregation Inhibitors

Fibrinolytic Agents
Cardiovascular Diseases
Cardiovascular Agents
Infection
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009