Inhaled Nitric Oxide Study for Respiratory Failure in Newborns

Respiratory Insufficiency Clinical Trial

— NINOS  

Official title:

The Randomized Inhaled Nitric Oxide Study (NINOS) in Full-Term and Nearly Full-Term Infants With Hypoxic Respiratory Failure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00005776
• Other study ID #: NICHD-NRN-0014
• Secondary ID: U01HD019897U10HD
• Status: Terminated
• Phase: Phase 3
• First received: June 1, 2000
• Last updated: September 22, 2017
• Start date: October 1995
• Est. completion date: May 1998

Study information

• Verified date: September 2017
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 235
• Est. completion date: May 1998
• Est. primary completion date: May 1996
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 14 Days

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Inhaled nitric oxide
Inhaled Nitric oxide at a concentration of 20 ppm
• Placebo
100% Oxygen

Locations

Country	Name	City	State
Canada	Foothills Hospital	Calgary	Alberta
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Université de Sherbrooke,	Sherbrooke,	Quebec
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	Health Sciences Center	Winnipeg	Manitoba
United States	University of New Mexico	Albuquerque	New Mexico
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Wayne State University	Detroit	Michigan
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Tennessee	Memphis	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	George Washington University	Washington, D.C.	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Medical Research Council of Canada, National Center for Research Resources (NCRR)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. The Neonatal Inhaled Nitric Oxide Study Group (NINOS). Pediatrics. 1997 Jun;99(6):838-45. — View Citation

Inhaled nitric oxide in term and near-term infants: neurodevelopmental follow-up of the neonatal inhaled nitric oxide study group (NINOS). J Pediatr. 2000 May;136(5):611-7. — View Citation

Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med. 1997 Feb 27;336(9):597-604. Erratum in: N Engl J Med 1997 Aug 7;337(6):434. — View Citation

Sokol GM, Ehrenkranz RA. Inhaled nitric oxide therapy in neonatal hypoxic respiratory failure: insights beyond primary outcomes. Semin Perinatol. 2003 Aug;27(4):311-9. Review. — View Citation

Sokol GM, Fineberg NS, Wright LL, Ehrenkranz RA. Changes in arterial oxygen tension when weaning neonates from inhaled nitric oxide. Pediatr Pulmonol. 2001 Jul;32(1):14-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death or initiation of ECMO		Before hospital discharge or 120 days of life
Secondary	PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient		30 minutes after drug administration
Secondary	Neurodevelopmental outcome		18-22 Months Corrected Age
Secondary	Duration of hospital stay		At hospital discharge
Secondary	Duration of assisted ventilation, air leaks, or chronic lung disease		At hospital discharge
Secondary	Transfers for ECMO		At hospital discharge
Secondary	Meeting ECMO criteria		At hospital discharge

External Links

•   NICHD Neonatal Research Network