Inhaled Nitric Oxide Study for Respiratory Failure in Newborns

Phase 3

Terminated

• Conditions: Pneumonia, Aspiration; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Persistent Fetal Circulation Syndrome; Infant, Newborn; Hypertension, Pulmonary
• Interventions: Drug: Inhaled nitric oxide; Drug: Placebo

• Registration Number: NCT00005776
• Lead Sponsor: NICHD Neonatal Research Network

Brief Summary

Respiratory failure in term newborns is associated with increased rates of death and long-term neurodevelopmental problems. This large international multicenter trial randomized newborns who had failed to respond to intensive care, including high levels of ventilator support, to receive either inhaled nitric oxide (iNO) or 100 percent oxygen to test whether iNO would decrease their risk of dying or requiring temporary lung bypass. Infants were followed during their initial hospitalization; their outcome was assessed at 18 to 24 mos of age.

Detailed Description

Respiratory failure in term newborns is associated with significant morbidity and mortality, despite maximal conventional therapy. Neonates with pulmonary hypertension have been treated with iNO, a selective pulmonary vasodilator. This multicenter, double-masked placebo-controlled randomized trial tested whether iNO would reduce the risk of death and/or the initiation of extracorporeal membrane oxygenation (ECMO) in a prospectively defined cohort of term or near-term neonates with hypoxic respiratory failure unresponsive to conventional therapy. The sample size was based on a reduction of the primary event (death or ECMO) from 50 percent to 30 percent; 90 percent power; and a two-tailed Type I error of 0.05.

Infants were evaluated at baseline for pulmonary, cardiac, bleeding status, and therapies received. Those who were greater than 34 wks gestation and 14 days old or less and required assisted ventilation with an OI (mean airway pressure x FiO2 divided by the PaO2 x 100) greater than 25 were eligible. They were randomly assigned to receive iNO at 20 ppm or 100 percent oxygen as a control. Infants whose PaO2 increased by less than 20 mm Hg after 30 minutes were studied at 80ppm iNO or control gas.; MetHg and NO2 concentrations were monitored regularly. Management, including surfactant administration, included prospectively defined criteria for study gas response, escalation, reinitiation, and weaning. The maximum total time on study gas was 336 hrs (after 240 hrs, the INO concentration was required to be no more than 5 ppm). Patients were followed to death, discharge, or 120 days and evaluated at 18-24 mos by a masked certified examiner.

Study Timeline

• Study Start: 1995-10
• Primary Completion: 1996-05
• Study Completion: 1998-05
• Study First Submitted: 2000-06-01
• Study First Submitted QC: 2000-06-01
• Study First Posted: 2000-06-02
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-22
• Last Update Posted: 2017-09-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 235

Inclusion Criteria

• Greater than 34 wks gestational age
• One or more of the following diagnoses: primary pulmonary hypertension of the newborn, respiratory distress syndrome, perinatal aspiration syndrome, pneumonia/sepsis, suspected pulmonary hypoplasia
• Oxygenation Index (OI) greater than 15 and less than 25 on 2 arterial blood gases at least 15 min apart
• Indwelling arterial line
• Echocardiography before randomization
• Parental consent

Exclusion Criteria

• Congenital diaphragmatic hernia
• Known congenital heart disease
• Decision not to provide full therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inhaled Nitric Oxide	Inhaled nitric oxide	Inhaled Nitric Oxide (iNO)
Oxygen	Placebo	100% oxygen

Primary Outcome Measures

Name	Time	Method
Death or initiation of ECMO	Before hospital discharge or 120 days of life

Secondary Outcome Measures

Name	Time	Method
Duration of assisted ventilation, air leaks, or chronic lung disease	At hospital discharge
Transfers for ECMO	At hospital discharge
Meeting ECMO criteria	At hospital discharge
PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient	30 minutes after drug administration
Neurodevelopmental outcome	18-22 Months Corrected Age
Duration of hospital stay	At hospital discharge

Trial Locations

Locations (20)

Case Western Reserve University, Rainbow Babies and Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Children's Hospital of Eastern Ontario; 🇨🇦 Ottawa, Ontario, Canada

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Cincinnati Children's Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Royal Alexandra Hospital; 🇨🇦 Edmonton, Alberta, Canada

Montreal Children's Hospital; 🇨🇦 Montreal, Quebec, Canada

Université de Sherbrooke,; 🇨🇦 Sherbrooke,, Quebec, Canada

Health Sciences Center; 🇨🇦 Winnipeg, Manitoba, Canada

Stanford University; 🇺🇸 Palo Alto, California, United States

George Washington University; 🇺🇸 Washington, D.C., District of Columbia, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

University of Tennessee; 🇺🇸 Memphis, Tennessee, United States

University of New Mexico; 🇺🇸 Albuquerque, New Mexico, United States

Brown University, Women & Infants Hospital of Rhode Island; 🇺🇸 Providence, Rhode Island, United States

Royal University Hospital; 🇨🇦 Saskatoon, Saskatchewan, Canada

McMaster University; 🇨🇦 Hamilton, Ontario, Canada

British Columbia Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Foothills Hospital; 🇨🇦 Calgary, Alberta, Canada