We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Inhaled Nitric Oxide Study for Respiratory Failure in Newborns (NINOS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00005776
Recruitment Status : Terminated (Results showed statistically significant benefit in the experimental group)
First Posted : June 2, 2000
Last Update Posted : September 26, 2017
Medical Research Council of Canada
National Center for Research Resources (NCRR)
Information provided by:
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.

Condition or disease Intervention/treatment Phase
Infant, Newborn Hypertension, Pulmonary Persistent Fetal Circulation Syndrome Pneumonia, Aspiration Respiratory Distress Syndrome, Newborn Respiratory Insufficiency Drug: Inhaled nitric oxide Drug: Placebo Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 235 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Randomized Inhaled Nitric Oxide Study (NINOS) in Full-Term and Nearly Full-Term Infants With Hypoxic Respiratory Failure
Study Start Date : October 1995
Actual Primary Completion Date : May 1996
Actual Study Completion Date : May 1998

Arm Intervention/treatment
Experimental: Inhaled Nitric Oxide
Inhaled Nitric Oxide (iNO)
Drug: Inhaled nitric oxide
Inhaled Nitric oxide at a concentration of 20 ppm

Placebo Comparator: Oxygen
100% oxygen
Drug: Placebo
100% Oxygen

Primary Outcome Measures :
  1. Death or initiation of ECMO [ Time Frame: Before hospital discharge or 120 days of life ]

Secondary Outcome Measures :
  1. PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient [ Time Frame: 30 minutes after drug administration ]
  2. Neurodevelopmental outcome [ Time Frame: 18-22 Months Corrected Age ]
  3. Duration of hospital stay [ Time Frame: At hospital discharge ]
  4. Duration of assisted ventilation, air leaks, or chronic lung disease [ Time Frame: At hospital discharge ]
  5. Transfers for ECMO [ Time Frame: At hospital discharge ]
  6. Meeting ECMO criteria [ Time Frame: At hospital discharge ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   up to 14 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00005776

Show Show 20 study locations
Sponsors and Collaborators
NICHD Neonatal Research Network
Medical Research Council of Canada
National Center for Research Resources (NCRR)
Layout table for investigator information
Study Director: Richard A. Ehrenkranz, MD Yale University
Principal Investigator: David K. Stevenson, MD Stanford University
Principal Investigator: Raymond Bain, PhD George Washington University
Principal Investigator: James A. Lemons, MD Indiana University
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Lu-Ann Papile, MD University of New Mexico
Principal Investigator: Edward F. Donovan, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Avroy A. Fanaroff, MD Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: William William Oh, MD Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: Sheldon B. Korones, MD University of Tennessee
Principal Investigator: Mary Wearden, MD Baylor College of Medicine
Principal Investigator: N. Singhal, MD Foothills Hospital, Calgary, Canada
Principal Investigator: Neil N. Finer, MD Royal Alexandra Hospital
Principal Investigator: A. Solimano, MD British Columbia Children's Hospital
Principal Investigator: C. Fajardo, MD Health Sciences Center, Winnipeg, Manitoba
Principal Investigator: H. Kirpalani, MD McMaster University
Principal Investigator: R. Walker, MD Children's Hospital of Eastern Ontario
Principal Investigator: A. Johnston, MD Montreal Children's Hospital of the MUHC
Principal Investigator: P. Blanchard, MD Université de Sherbrooke, Sherbrooke, Quebec
Principal Investigator: K. Sankarhan, MD Royal University Hospital, Saskatoon, Saskatchewan
Additional Information:
Publications of Results:
Layout table for additonal information
Responsible Party: Richard A. Ehrenkranz, NRN Lead Study Investigator, Yale University School of Medicine
ClinicalTrials.gov Identifier: NCT00005776    
Other Study ID Numbers: NICHD-NRN-0014
U01HD019897 ( U.S. NIH Grant/Contract )
U10HD021364 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD021397 ( U.S. NIH Grant/Contract )
U10HD021415 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD027881 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD034167 ( U.S. NIH Grant/Contract )
U10HD034216 ( U.S. NIH Grant/Contract )
M01RR000070 ( U.S. NIH Grant/Contract )
M01RR000750 ( U.S. NIH Grant/Contract )
M01RR000997 ( U.S. NIH Grant/Contract )
M01RR001032 ( U.S. NIH Grant/Contract )
M01RR006022 ( U.S. NIH Grant/Contract )
M01RR008084 ( U.S. NIH Grant/Contract )
First Posted: June 2, 2000    Key Record Dates
Last Update Posted: September 26, 2017
Last Verified: September 2017
Keywords provided by NICHD Neonatal Research Network:
NICHD Neonatal Research Network
Hypertension, pulmonary
Hypoxic respiratory failure
Meconium aspiration
Nitric oxide
Oxygen inhalation therapy
Persistent Fetal Circulation Syndrome
Pneumonia, aspiration
Respiratory distress syndrome
Respiratory insufficiency
Severe respiratory failure
Additional relevant MeSH terms:
Layout table for MeSH terms
Pneumonia, Aspiration
Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Insufficiency
Hypertension, Pulmonary
Persistent Fetal Circulation Syndrome
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Infections
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action