Inhaled Nitric Oxide Study for Respiratory Failure in Newborns

NCT00005776 | Terminated Phase 3 DMC

• 22 other identifiers: NICHD-NRN-0014U01HD019897U10HD021364U10HD021373U10HD021385U10HD021397U10HD021415U10HD027851U10HD027853U10HD027856U10HD027871U10HD027880U10HD027881U10HD027904U10HD034167U10HD034216M01RR000070M01RR000750M01RR000997M01RR001032M01RR006022M01RR008084
• Study Type: interventional
• Target: 235
• Locations: 2 countries
• Sites: 20

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Death or initiation of ECMO

  Before hospital discharge or 120 days of life

Secondary Outcomes (6)

• PaO2 levels, oxygenation index, and alveolar-arterial oxygen gradient

  30 minutes after drug administration

• Neurodevelopmental outcome

  18-22 Months Corrected Age

• Duration of hospital stay

  At hospital discharge

• Duration of assisted ventilation, air leaks, or chronic lung disease

  At hospital discharge

• Transfers for ECMO

  At hospital discharge

Study Arms (2)

Inhaled Nitric Oxide

EXPERIMENTAL

Inhaled Nitric Oxide (iNO)

Drug: Inhaled nitric oxide

Oxygen

PLACEBO COMPARATOR

100% oxygen

Drug: Placebo

Interventions

Inhaled nitric oxide DRUG

Inhaled Nitric oxide at a concentration of 20 ppm

Inhaled Nitric Oxide

Placebo DRUG

100% Oxygen

Oxygen

Eligibility Criteria

• Age: Up to 14 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Congenital diaphragmatic hernia
• Known congenital heart disease
• Decision not to provide full therapy

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• Medical Research Council of Canada: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (20)

Stanford University

Palo Alto, California, 94304, United States

Location

Yale University

New Haven, Connecticut, 06504, United States

Location

George Washington University

Washington D.C., District of Columbia, 20052, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

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

Cleveland, Ohio, 44106, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Tennessee

Memphis, Tennessee, 38163, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Foothills Hospital

Calgary, Alberta, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Location

Health Sciences Center

Winnipeg, Manitoba, Canada

Location

McMaster University

Hamilton, Ontario, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, Canada

Location

Université de Sherbrooke,

Sherbrooke, Quebec, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Location

Related Publications (5)

• 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.

  PMID: 9036320 RESULT

• 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.

  PMID: 9190553 RESULT

• 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.

  PMID: 10802492 RESULT

• 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.

  PMID: 11416871 RESULT

• 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.

  PMID: 14510322 RESULT

Related Links

• NICHD Neonatal Research Network

MeSH Terms

Conditions

Hypertension, Pulmonary; Persistent Fetal Circulation Syndrome; Pneumonia, Aspiration; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Meconium Aspiration Syndrome; Methemoglobinemia; Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pneumonia; Respiratory Tract Infections; Infections; Respiration Disorders; Infant, Premature, Diseases; Lung Injury; Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Richard A. Ehrenkranz, MD

  Yale University

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: June 1, 2000
• First Posted: June 2, 2000
• Study Start: October 1, 1995
• Primary Completion: May 1, 1996
• Study Completion: May 1, 1998
• Last Updated: September 26, 2017

Record last verified: 2017-09

Locations

CA (9); US (11)