Early Inhaled Nitric Oxide for Respiratory Failure in Newborns

Summary

This prospective, randomized controlled trial tested whether initiating iNO therapy earlier would reduce death and reduce the use of extracorporeal membrane oxygenation (ECMO) -- temporary lung bypass -- therapy compared with the standard recommendation threshold. Infants who were born at \>34 weeks' gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) \>15 and \<25 on any 2 measurements in a 12-hour interval. Infants were randomized to receive either early iNO or to simulated initiation of iNO (control). Infants who had an increase in OI to 25 or more were given iNO as standard therapy. The neurodevelopment of the subjects were evaluated at 18-22 months corrected age.

Conditions

• Infant, Newborn
• Hypertension, Pulmonary
• Persistent Fetal Circulation Syndrome
• Pneumonia, Aspiration
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency

Interventions

DRUG

Inhaled Nitric Oxide

Study gas was initiated at a concentration of 5 ppm, and the dose was increased to 20 ppm when the infant had \<=20 mm Hg increase in PaO2 (less than full response).

DRUG

Standard iNO therapy

Begin a sham initiation of iNO in term and near-term infants in respiratory failure with an oxygenation index (OI) between 15-25; initiated actual iNO therapy based on standard threshold (OI \>=25).

Sponsors & Collaborators

• National Center for Research Resources (NCRR)

  collaborator NIH

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Mallinckrodt

  collaborator INDUSTRY

• NICHD Neonatal Research Network

  lead NETWORK

Principal Investigators

• G. Ganesh Konduri, MD · University of Wisconsin, Madison

• Waldemar A. Carlo, MD · University of Alabama at Birmingham

• Carlos Fajardo, MD · St. Joseph's Hospital

• Krisa P. Van Meurs, MD · Stanford University

• Gail Knight, MD · San Diego Children's Hospital

• Richard A. Ehrenkranz, MD · Yale University

• Charles R. Bauer, MD · University of Miami

• Barbara J. Stoll, MD · Emory University

• Greg M. Sokol, MD · Indiana University

• Seetha Shankaran, MD · Wayne State University

• Lu-Ann Papile, MD · University of New Mexico

• Edward F. Donovan, MD · Children's Hospital Medical Center, Cincinnati

• Avroy A. Fanaroff, MD · Case Western Reserve University, Rainbow Babies and Children's Hospital

• William Oh, MD · Brown University, Women & Infants Hospital of Rhode Island

• Sheldon B. Korones, MD · University of Tennessee

• Abbot R. Laptook, MD · University of Texas, Southwestern Medical Center at Dallas

• Mary Wearden, MD · Baylor College of Medicine

• Kathleen A. Kennedy, MD MPH · The University of Texas Health Science Center, Houston

• Dennis E. Mayock, MD · University of Washington

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Max Age

14 Days

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1998-08-31

Primary Completion

2001-05-31

Completion

2003-08-31

Countries

• United States

Study Locations