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

Primary Purpose

Infant, Newborn, Hypertension, Pulmonary, Persistent Fetal Circulation Syndrome

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Inhaled nitric oxide
Placebo
Sponsored by
NICHD Neonatal Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infant, Newborn focused on measuring 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

Eligibility Criteria

undefined - 14 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford University
  • Yale University
  • George Washington University
  • Indiana University
  • Wayne State University
  • University of New Mexico
  • Cincinnati Children's Medical Center
  • Case Western Reserve University, Rainbow Babies and Children's Hospital
  • Brown University, Women & Infants Hospital of Rhode Island
  • University of Tennessee
  • Texas Children's Hospital
  • Foothills Hospital
  • Royal Alexandra Hospital
  • British Columbia Children's Hospital
  • Health Sciences Center
  • McMaster University
  • Children's Hospital of Eastern Ontario
  • Montreal Children's Hospital
  • Université de Sherbrooke,
  • Royal University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Inhaled Nitric Oxide

Oxygen

Arm Description

Inhaled Nitric Oxide (iNO)

100% oxygen

Outcomes

Primary Outcome Measures

Death or initiation of ECMO

Secondary Outcome Measures

PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient
Neurodevelopmental outcome
Duration of hospital stay
Duration of assisted ventilation, air leaks, or chronic lung disease
Transfers for ECMO
Meeting ECMO criteria

Full Information

First Posted
June 1, 2000
Last Updated
September 22, 2017
Sponsor
NICHD Neonatal Research Network
Collaborators
Medical Research Council of Canada, National Center for Research Resources (NCRR)
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1. Study Identification

Unique Protocol Identification Number
NCT00005776
Brief Title
Inhaled Nitric Oxide Study for Respiratory Failure in Newborns
Acronym
NINOS
Official Title
The Randomized Inhaled Nitric Oxide Study (NINOS) in Full-Term and Nearly Full-Term Infants With Hypoxic Respiratory Failure
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Terminated
Why Stopped
Results showed statistically significant benefit in the experimental group
Study Start Date
October 1995 (undefined)
Primary Completion Date
May 1996 (Actual)
Study Completion Date
May 1998 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
NICHD Neonatal Research Network
Collaborators
Medical Research Council of Canada, National Center for Research Resources (NCRR)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infant, Newborn, Hypertension, Pulmonary, Persistent Fetal Circulation Syndrome, Pneumonia, Aspiration, Respiratory Distress Syndrome, Newborn, Respiratory Insufficiency
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
235 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Inhaled Nitric Oxide
Arm Type
Experimental
Arm Description
Inhaled Nitric Oxide (iNO)
Arm Title
Oxygen
Arm Type
Placebo Comparator
Arm Description
100% oxygen
Intervention Type
Drug
Intervention Name(s)
Inhaled nitric oxide
Intervention Description
Inhaled Nitric oxide at a concentration of 20 ppm
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
100% Oxygen
Primary Outcome Measure Information:
Title
Death or initiation of ECMO
Time Frame
Before hospital discharge or 120 days of life
Secondary Outcome Measure Information:
Title
PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient
Time Frame
30 minutes after drug administration
Title
Neurodevelopmental outcome
Time Frame
18-22 Months Corrected Age
Title
Duration of hospital stay
Time Frame
At hospital discharge
Title
Duration of assisted ventilation, air leaks, or chronic lung disease
Time Frame
At hospital discharge
Title
Transfers for ECMO
Time Frame
At hospital discharge
Title
Meeting ECMO criteria
Time Frame
At hospital discharge

10. Eligibility

Sex
All
Maximum Age & Unit of Time
14 Days
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard A. Ehrenkranz, MD
Organizational Affiliation
Yale University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
David K. Stevenson, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Raymond Bain, PhD
Organizational Affiliation
George Washington University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James A. Lemons, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Seetha Shankaran, MD
Organizational Affiliation
Wayne State University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lu-Ann Papile, MD
Organizational Affiliation
University of New Mexico
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Edward F. Donovan, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Avroy A. Fanaroff, MD
Organizational Affiliation
Case Western Reserve University, Rainbow Babies and Children's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
William William Oh, MD
Organizational Affiliation
Brown University, Women & Infants Hospital of Rhode Island
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sheldon B. Korones, MD
Organizational Affiliation
University of Tennessee
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mary Wearden, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
N. Singhal, MD
Organizational Affiliation
Foothills Hospital, Calgary, Canada
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Neil N. Finer, MD
Organizational Affiliation
Royal Alexandra Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
A. Solimano, MD
Organizational Affiliation
British Columbia Children's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
C. Fajardo, MD
Organizational Affiliation
Health Sciences Center, Winnipeg, Manitoba
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
H. Kirpalani, MD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
R. Walker, MD
Organizational Affiliation
Children's Hospital of Eastern Ontario
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
A. Johnston, MD
Organizational Affiliation
Montreal Children's Hospital of the MUHC
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
P. Blanchard, MD
Organizational Affiliation
Université de Sherbrooke, Sherbrooke, Quebec
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
K. Sankarhan, MD
Organizational Affiliation
Royal University Hospital, Saskatoon, Saskatchewan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06504
Country
United States
Facility Name
George Washington University
City
Washington, D.C.
State/Province
District of Columbia
ZIP/Postal Code
20052
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Cincinnati Children's Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case Western Reserve University, Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Brown University, Women & Infants Hospital of Rhode Island
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
University of Tennessee
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Foothills Hospital
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Royal Alexandra Hospital
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
British Columbia Children's Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Health Sciences Center
City
Winnipeg
State/Province
Manitoba
Country
Canada
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Children's Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Montreal Children's Hospital
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Université de Sherbrooke,
City
Sherbrooke,
State/Province
Quebec
Country
Canada
Facility Name
Royal University Hospital
City
Saskatoon
State/Province
Saskatchewan
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
9036320
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. doi: 10.1056/NEJM199702273360901. Erratum In: N Engl J Med 1997 Aug 7;337(6):434.
Results Reference
result
PubMed Identifier
9190553
Citation
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. doi: 10.1542/peds.99.6.838.
Results Reference
result
PubMed Identifier
10802492
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. doi: 10.1067/mpd.2000.104826.
Results Reference
result
PubMed Identifier
11416871
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. doi: 10.1002/ppul.1083.
Results Reference
result
PubMed Identifier
14510322
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. doi: 10.1016/s0146-0005(03)00043-0.
Results Reference
result
Links:
URL
http://neonatal.rti.org
Description
NICHD Neonatal Research Network

Learn more about this trial

Inhaled Nitric Oxide Study for Respiratory Failure in Newborns

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