Inhaled Nitric Oxide Study for Respiratory Failure in Newborns

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

235 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-10-31

Study Completion Date

1998-05-31

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Inhaled Nitric Oxide

Inhaled Nitric Oxide (iNO)

Group Type EXPERIMENTAL

Inhaled nitric oxide

Intervention Type DRUG

Inhaled Nitric oxide at a concentration of 20 ppm

Oxygen

100% oxygen

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

100% Oxygen

Interventions

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Inhaled nitric oxide

Inhaled Nitric oxide at a concentration of 20 ppm

Intervention Type DRUG

Placebo

100% Oxygen

Intervention Type DRUG

Eligibility Criteria

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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

Maximum Eligible Age

14 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Yale University School of Medicine

Principal Investigators

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Richard A. Ehrenkranz, MD

Role: STUDY_DIRECTOR

Yale University

David K. Stevenson, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Raymond Bain, PhD

Role: PRINCIPAL_INVESTIGATOR

George Washington University

James A. Lemons, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Seetha Shankaran, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Lu-Ann Papile, MD

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico

Edward F. Donovan, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Avroy A. Fanaroff, MD

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University, Rainbow Babies and Children's Hospital

William William Oh, MD

Role: PRINCIPAL_INVESTIGATOR

Brown University, Women & Infants Hospital of Rhode Island

Sheldon B. Korones, MD

Role: PRINCIPAL_INVESTIGATOR

University of Tennessee

Mary Wearden, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

N. Singhal, MD

Role: PRINCIPAL_INVESTIGATOR

Foothills Hospital, Calgary, Canada

Neil N. Finer, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Alexandra Hospital

A. Solimano, MD

Role: PRINCIPAL_INVESTIGATOR

British Columbia Children's Hospital

C. Fajardo, MD

Role: PRINCIPAL_INVESTIGATOR

Health Sciences Center, Winnipeg, Manitoba

H. Kirpalani, MD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

R. Walker, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Eastern Ontario

A. Johnston, MD

Role: PRINCIPAL_INVESTIGATOR

Montreal Children's Hospital of the MUHC

P. Blanchard, MD

Role: PRINCIPAL_INVESTIGATOR

Université de Sherbrooke, Sherbrooke, Quebec

K. Sankarhan, MD

Role: PRINCIPAL_INVESTIGATOR

Royal University Hospital, Saskatoon, Saskatchewan

Locations

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Stanford University

Palo Alto, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

George Washington University

Washington D.C., District of Columbia, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

University of New Mexico

Albuquerque, New Mexico, United States

Site Status

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States

Site Status

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Site Status

University of Tennessee

Memphis, Tennessee, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Foothills Hospital

Calgary, Alberta, Canada

Site Status

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

Health Sciences Center

Winnipeg, Manitoba, Canada

Site Status

McMaster University

Hamilton, Ontario, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

Université de Sherbrooke,

Sherbrooke, Quebec, Canada

Site Status

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type RESULT

PMID: 9036320 (View on PubMed)

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.

Reference Type RESULT

PMID: 9190553 (View on PubMed)

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.

Reference Type RESULT

PMID: 10802492 (View on PubMed)

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.

Reference Type RESULT

PMID: 11416871 (View on PubMed)

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.

Reference Type RESULT

PMID: 14510322 (View on PubMed)