Inhaled PGE1 in Neonatal Hypoxemic Respiratory Failure

Pulmonary Hypertension Clinical Trial

— IPGE1  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00598429
• Other study ID #: NICHD-NRN-0037
• Secondary ID: U10HD036790U10HD
• Status: Withdrawn
• Phase: Phase 2
• Start date: May 2008
• Est. completion date: September 2008

Study information

• Verified date: July 2015
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 7 Days

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Infant, Newborn
• Pulmonary Hypertension
• Pulmonary Valve Insufficiency
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency
• Streptococcal Infections

Intervention

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

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Iowa	Iowa City	Iowa
United States	Stanford University	Palo Alto	California
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   NICHD Neonatal Research Network