Clinical trial NCT00598429: Inhaled PGE1 in Neonatal Hypoxemic Respiratory Failure
Official title: Randomized Clinical Trial of Inhaled PGE1 (IPGE1) in Neonatal Hypoxemic Respiratory Failure. A Protocol for the NICHD Neonatal Research Network
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Infant, Newborn
Respiratory Insufficiency
Pulmonary Hypertension
Respiratory Distress Syndrome, Newborn
Streptococcal Infections
Keywords: NICHD Neonatal Research Network
Hypoxemic respiratory failure (HRF)
Persistent pulmonary hypertension of the newborn (PPHN)
Prostaglandin E1 (PGE1)
Mechanical ventilation
Meconium, aspiration
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2008-01-21
Enrollment: 0
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: The ability to recruit an adequate number of patients (n = 50) in a 6-9 month period without excessive (>20%) protocol violations.
timeFrame: 6-9 months after trial begins recruitment
Secondary outcomes:
measure: Progression to an OI greater than 25
timeFrame: 72-hours after enrollment
measure: Improvement in partial pressure of oxygen (PaO2) in the blood gas
timeFrame: 72-hours after enrollment
measure: Change in OI
timeFrame: 72 hours after enrollment
measure: Death
timeFrame: 72-hours after intervention
measure: Need for inhaled nitric oxide or ECMO
timeFrame: 72-hours after enrollment
measure: Length of hospitalization
measure: Duration of mechanical ventilation
measure: Number of days of oxygen used and need for supplemental oxygen at 28 days of life
measure: Occurrence of grade III-IV intracranial hemorrhage and cystic leukomalacia
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Case Western Reserve University, Rainbow Babies and Children's Hospital
name: Michele C. Walsh, MD MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Ronald N. Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Krisa P. Van Meurs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts Medical Center
name: Ivan D. Frantz III, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemar A. Carlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Edward F. Bell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Kristi L. Watterberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Roger G. Faix, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Pablo J. Sanchez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.