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

This study has been terminated.
(Results showed statistically significant benefit in the experimental group)
Sponsor:
Collaborators:
Medical Research Council of Canada
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00005776
First received: June 1, 2000
Last updated: January 9, 2011
Last verified: September 2010
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Death or initiation of ECMO [ Time Frame: Before hospital discharge or 120 days of life ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient [ Time Frame: 30 minutes after drug administration ] [ Designated as safety issue: Yes ]
  • Neurodevelopmental outcome [ Time Frame: 18-22 Months Corrected Age ] [ Designated as safety issue: No ]
  • Duration of hospital stay [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
  • Duration of assisted ventilation, air leaks, or chronic lung disease [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
  • Transfers for ECMO [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
  • Meeting ECMO criteria [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]

Enrollment: 235
Study Start Date: October 1995
Study Completion Date: May 1998
Primary Completion Date: May 1996 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 14 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005776

  Show 20 Study Locations
Sponsors and Collaborators
Medical Research Council of Canada
Investigators
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 Cincinnati Children's Medical Center
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 Texas Children's Hospital
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
  More Information

Additional Information:
Publications:
Responsible Party: Richard A. Ehrenkranz, NRN Lead Study Investigator, Yale University School of Medicine
ClinicalTrials.gov Identifier: NCT00005776     History of Changes
Other Study ID Numbers: NICHD-NRN-0014, U01HD019897, U10HD021364, U10HD021373, U10HD021385, U10HD021397, U10HD021415, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027881, U10HD027904, U10HD034167, U10HD034216, M01RR000070, M01RR000750, M01RR000997, M01RR001032, M01RR006022, M01RR008084
Study First Received: June 1, 2000
Last Updated: January 9, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Hypertension, pulmonary
Hypoxic respiratory failure
Meconium aspiration
Methemoglobinemia
Nitric oxide
Oxygen inhalation therapy
Persistent Fetal Circulation Syndrome
Pneumonia, aspiration
Respiratory distress syndrome
Respiratory insufficiency
Severe respiratory failure

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Persistent Fetal Circulation Syndrome
Pneumonia
Pneumonia, Aspiration
Respiratory Distress Syndrome, Newborn
Respiratory Insufficiency
Syndrome
Cardiovascular Diseases
Disease
Infant, Newborn, Diseases
Infant, Premature, Diseases
Lung Diseases
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Respiratory Tract Infections
Vascular Diseases
Nitric Oxide
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on October 29, 2014