Inhaled PGE1 in Neonatal Hypoxemic Respiratory Failure (IPGE1)

• ClinicalTrials.gov Identifier: NCT00598429
• Recruitment Status: Withdrawn
• First Posted: January 21, 2008
• Last Update Posted: March 22, 2019
• Sponsor: NICHD Neonatal Research Network
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): NICHD Neonatal Research Network

Study Description

Brief 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.

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

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: May 2008
• Actual Primary Completion Date: September 2008
• Actual Study Completion Date: September 2008

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. Progression to an OI greater than 25 [ Time Frame: 72-hours after enrollment ]
2. Improvement in partial pressure of oxygen (PaO2) in the blood gas [ Time Frame: 72-hours after enrollment ]
3. Change in OI [ Time Frame: 72 hours after enrollment ]
4. Death [ Time Frame: 72-hours after intervention ]
5. Need for inhaled nitric oxide or ECMO [ Time Frame: 72-hours after enrollment ]
6. Length of hospitalization
7. Duration of mechanical ventilation
8. Number of days of oxygen used and need for supplemental oxygen at 28 days of life
9. Occurrence of grade III-IV intracranial hemorrhage and cystic leukomalacia

Eligibility Criteria

• Ages Eligible for Study: up to 7 Days (Child)
• Sexes Eligible for Study: All
• 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

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

RTI International

Durham, North Carolina, United States, 27705

Duke University

Durham, North Carolina, United States, 27710

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

NICHD Neonatal Research Network

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

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:

NICHD Neonatal Research Network 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: NICHD Neonatal Research Network
• ClinicalTrials.gov Identifier: NCT00598429
• 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 )
• First Posted: January 21, 2008
• Last Update Posted: March 22, 2019
• Last Verified: July 2015

Keywords provided by NICHD Neonatal Research Network:

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:

Streptococcal Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Hypertension, Pulmonary; Respiratory Insufficiency; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Alprostadil; Platelet Aggregation Inhibitors; Vasodilator Agents; Urological Agents