Early Inhaled Nitric Oxide for Respiratory Failure in Newborns

NCT00005773 | Terminated Phase 3 DMC

• 24 other identifiers: NICHD-NRN-0019U01HD019897U10HD021364U10HD021373U10HD021385U10HD021397U10HD021415U10HD027853U10HD027856U10HD027871U10HD027880U10HD027881U10HD027904U10HD034167U10HD034216U10HD040689M01RR000070M01RR000633M01RR000750M01RR000997M01RR001032M01RR006022M01RR008084M01RR016587
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 18

Brief Summary

This prospective, randomized controlled trial tested whether initiating iNO therapy earlier would reduce death and reduce the use of extracorporeal membrane oxygenation (ECMO) -- temporary lung bypass -- therapy compared with the standard recommendation threshold. Infants who were born at \>34 weeks' gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) \>15 and \<25 on any 2 measurements in a 12-hour interval. Infants were randomized to receive either early iNO or to simulated initiation of iNO (control). Infants who had an increase in OI to 25 or more were given iNO as standard therapy. The neurodevelopment of the subjects were evaluated at 18-22 months corrected 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 use of extracorporeal membrane oxygenation (ECMO)

  Hospital discharge or 120 days of life

Secondary Outcomes (3)

• Use of iNO therapy based on the standard recommended threshold

  Hospital Discharge or 120 days of life

• Progression to severe respiratory failure (OI>40)

  Hospital discharge or 120 days of life

• Neurodevelopmental impairment

  18-22 months corrected age

Study Arms (2)

Early iNO Management

EXPERIMENTAL

Initiation of iNO in use for term and near-term infants in respiratory failure with an oxygenation index between 15-25.

Drug: Inhaled Nitric Oxide

Standard iNO management

ACTIVE COMPARATOR

Begin a sham initiation of iNO in term and near-term infants in respiratory failure with an oxygenation index (OI) between 15-25; initiated actual iNO therapy based on standard threshold (OI \>=25).

Drug: Standard iNO therapy

Interventions

Inhaled Nitric Oxide DRUG

Study gas was initiated at a concentration of 5 ppm, and the dose was increased to 20 ppm when the infant had \<=20 mm Hg increase in PaO2 (less than full response).

Early iNO Management

Standard iNO therapy DRUG

Begin a sham initiation of iNO in term and near-term infants in respiratory failure with an oxygenation index (OI) between 15-25; initiated actual iNO therapy based on standard threshold (OI \>=25).

Standard iNO management

Eligibility Criteria

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

You may qualify if:

• Infants born at \>34 weeks gestational age
• Require assisted ventilation for hypoxic respiratory failure
• Have a diagnosis of primary persistent pulmonary hypertension (PPHN), respiratory distress syndrome, perinatal aspiration syndrome, pneumonia/sepsis, or suspected pulmonary hypoplasia
• Have an oxygenation index \>15 and \<25 based on 2 arterial blood gases taken at least 15 minutes apart or an Fi02 \>80%
• In-dwelling arterial line
• Parental consent

You may not qualify if:

• Known structural congenital heart disease, except patent ductus arteriosus and atrial level shunts
• Congenital diaphragmatic hernia
• Use of high frequency jet ventilation at the time of randomization
• Prior exposure to inhaled nitric oxide therapy

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Center for Research Resources (NCRR): collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Mallinckrodt: collaborator

Study Sites (18)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

St. Joseph's Hospital

Phoenix, Arizona, 85013, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

San Diego Children's Hospital

San Diego, California, 92130, United States

Location

Yale University

New Haven, Connecticut, 06504, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30303, 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

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98195, United States

Location

Related Publications (4)

• Sokol GM, Van Meurs KP, Wright LL, Rivera O, Thorn WJ 3rd, Chu PM, Sams RL. Nitrogen dioxide formation during inhaled nitric oxide therapy. Clin Chem. 1999 Mar;45(3):382-7.

  PMID: 10053039 BACKGROUND

• 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 BACKGROUND

• Konduri GG, Solimano A, Sokol GM, Singer J, Ehrenkranz RA, Singhal N, Wright LL, Van Meurs K, Stork E, Kirpalani H, Peliowski A; Neonatal Inhaled Nitric Oxide Study Group. A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure. Pediatrics. 2004 Mar;113(3 Pt 1):559-64. doi: 10.1542/peds.113.3.559.

  PMID: 14993550 RESULT

• Konduri GG, Vohr B, Robertson C, Sokol GM, Solimano A, Singer J, Ehrenkranz RA, Singhal N, Wright LL, Van Meurs K, Stork E, Kirpalani H, Peliowski A, Johnson Y; Neonatal Inhaled Nitric Oxide Study Group. Early inhaled nitric oxide therapy for term and near-term newborn infants with hypoxic respiratory failure: neurodevelopmental follow-up. J Pediatr. 2007 Mar;150(3):235-40, 240.e1. doi: 10.1016/j.jpeds.2006.11.065.

  PMID: 17307536 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

• G. Ganesh Konduri, MD

  University of Wisconsin, Madison

  STUDY DIRECTOR

• Waldemar A. Carlo, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Carlos Fajardo, MD

  St. Joseph's Hospital

  PRINCIPAL INVESTIGATOR

• Krisa P. Van Meurs, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Gail Knight, MD

  San Diego Children's Hospital

  PRINCIPAL INVESTIGATOR

• Richard A. Ehrenkranz, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Charles R. Bauer, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Barbara J. Stoll, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Greg M. Sokol, 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

  STUDY DIRECTOR

• William Oh, MD

  Brown University, Women & Infants Hospital of Rhode Island

  PRINCIPAL INVESTIGATOR

• Sheldon B. Korones, MD

  University of Tennessee

  PRINCIPAL INVESTIGATOR

• Abbot R. Laptook, MD

  University of Texas, Southwestern Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

• Mary Wearden, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Kathleen A. Kennedy, MD MPH

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Dennis E. Mayock, MD

  University of Washington

  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: August 1, 1998
• Primary Completion: May 1, 2001
• Study Completion: August 1, 2003
• Last Updated: September 26, 2017

Record last verified: 2017-09

Locations

US (18)