Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00006401
First received: October 12, 2000
Last updated: May 7, 2013
Last verified: October 2012
  Purpose

To determine whether or not inhaled nitric oxide (iNO) safely decreases the incidence of chronic lung disease (CLD) in premature infants.


Condition Intervention Phase
Lung Diseases
Bronchopulmonary Dysplasia
Drug: iNO
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Inhaled NO for the Prevention of Chronic Lung Disease

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Participant's survival without CLD (measured at 36 weeks after birth)

Estimated Enrollment: 793
Study Start Date: September 2000
Study Completion Date: October 2007
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inhaled Nitric Oxide (iNO)
Nitric Oxide study gas will be initiated at 5 ppm using the INOvent delivery system. The delivery system provides for masked delivery of the treatment gas. This dose will be used for a 21-day period or until extubation.
Drug: iNO
Other Name: Inhaled nitric oxide.
Placebo Comparator: Placebo

Detailed Description:

BACKGROUND:

Despite advances in medical, nursing, and respiratory care, CLD affects up to 50 percent of premature infants. As a result, nearly 50,000 infants in the United States develop CLD. It is desirable to investigate therapies that decrease the incidence of CLD because it is associated with failure to thrive, developmental delay, increased risk of pulmonary infection, reactive airway disease, pulmonary hypertension, and death.

DESIGN NARRATIVE:

This is a randomized, double-blind, placebo-controlled, multi-center study. Three specific hypotheses will be tested: 1) iNO reduces the incidence of CLD; 2) iNO reduces serum and lung (tracheal aspirate) markers of inflammation; and 3) iNO does not increase the incidence of intraventricular hemorrhage in premature neonates. The primary endpoint is survival without CLD (defined as continued oxygen requirement) at 36 weeks post conceptional age.

A total of 793 premature newborns will be enrolled from 14 centers within 48 hours of birth. They will be randomly assigned to receive either placebo or iNO at 5 ppm until the breathing tube can be safely removed or after 21 days. The iNO will be delivered by an INOvent delivery system in such a way that physicians and nurses will not know which treatment each participant is receiving. Management strategies for aspects of patient care including mechanical ventilation, surfactant administration, fluid administration, and steroid use will be determined by physicians at each center. Serial cranial ultrasounds and methemoglobin levels will be monitored to determine adverse events. The first 200 patients will have serial blood samples and tracheal aspirates obtained for measurements of inflammatory mediators, including interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), endothelin-1, myeloperoxidase, neutrophil counts (tracheal aspirates), and endothelin-1 (blood). Participants will be seen at 12 and 24 months of age to monitor the long-term effects on the cardiopulmonary or neurologic systems. At these visits, a health questionnaire will be administered and Bayley II scales of infant development will be completed.

  Eligibility

Ages Eligible for Study:   up to 1 Year
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Weighing between 500 to 1250 grams at birth
  • Gestational age of less than 34 weeks
  • Less than 48 hours old
  • Respiratory failure on mechanical ventilation
  • Absence of structural heart disease (PDA, ASD less than 1 cm, or VSD less than 2 mm are permitted if known prior to study entry)
  • Absence of lethal congenital anomaly

Exclusion Criteria:

  • Concurrent participation in another experimental study (observational studies will be allowed with prior approval by the Steering Committee and Data and Safety Monitoring Board)
  • Active pulmonary hemorrhage
  • Unevaluated pneumothorax
  • High frequency jet ventilation
  • Expected short duration of ventilation (less than 48 hours from birth)
  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: NCT00006401

Locations
United States, Arizona
St. Joseph's Hospital
Phoenix, Arizona, United States, 85013
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92350
Univeristy of Southern California/Good Samaritan Hospital
Los Angeles, California, United States, 90033
United States, Colorado
Children's Hospital
Denver, Colorado, United States, 80218-1088
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030
United States, Iowa
University of Iowa Hospital & Clinics
Iowa City, Iowa, United States, 52242
United States, North Carolina
University of North Carolina Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oklahoma
Children's Hospital of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19107
Magee-Women's Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Utah
Utah Valley Regional Medical Center
Provo, Utah, United States, 84604
Sponsors and Collaborators
Investigators
Study Chair: John P. Kinsella, MD Children's Hospital Medical Center, Cincinnati
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00006401     History of Changes
Other Study ID Numbers: 135, U01 HL64857
Study First Received: October 12, 2000
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Diseases
Bronchopulmonary Dysplasia
Respiratory Tract Diseases
Ventilator-Induced Lung Injury
Lung Injury
Infant, Premature, Diseases
Infant, Newborn, Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on September 18, 2014