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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. 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

Tracking Information
First Submitted Date  ICMJE June 1, 2000
First Posted Date  ICMJE June 2, 2000
Last Update Posted Date September 26, 2017
Study Start Date  ICMJE October 1995
Actual Primary Completion Date May 1996   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2009)
Death or initiation of ECMO [ Time Frame: Before hospital discharge or 120 days of life ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2009)
  • PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient [ Time Frame: 30 minutes after drug administration ]
  • Neurodevelopmental outcome [ Time Frame: 18-22 Months Corrected Age ]
  • Duration of hospital stay [ Time Frame: At hospital discharge ]
  • Duration of assisted ventilation, air leaks, or chronic lung disease [ Time Frame: At hospital discharge ]
  • Transfers for ECMO [ Time Frame: At hospital discharge ]
  • Meeting ECMO criteria [ Time Frame: At hospital discharge ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Inhaled Nitric Oxide Study for Respiratory Failure in Newborns
Official Title  ICMJE The Randomized Inhaled Nitric Oxide Study (NINOS) in Full-Term and Nearly Full-Term Infants With Hypoxic Respiratory Failure
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Infant, Newborn
  • Hypertension, Pulmonary
  • Persistent Fetal Circulation Syndrome
  • Pneumonia, Aspiration
  • Respiratory Distress Syndrome, Newborn
  • Respiratory Insufficiency
Intervention  ICMJE
  • Drug: Inhaled nitric oxide
    Inhaled Nitric oxide at a concentration of 20 ppm
  • Drug: Placebo
    100% Oxygen
Study Arms  ICMJE
  • Experimental: Inhaled Nitric Oxide
    Inhaled Nitric Oxide (iNO)
    Intervention: Drug: Inhaled nitric oxide
  • Placebo Comparator: Oxygen
    100% oxygen
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 23, 2005)
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 1998
Actual Primary Completion Date May 1996   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 14 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00005776
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard A. Ehrenkranz, NRN Lead Study Investigator, Yale University School of Medicine
Study Sponsor  ICMJE NICHD Neonatal Research Network
Collaborators  ICMJE
  • Medical Research Council of Canada
  • National Center for Research Resources (NCRR)
Investigators  ICMJE
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
PRS Account NICHD Neonatal Research Network
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP