Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants
- Conditions
- Lung DiseasesBronchopulmonary Dysplasia
- Interventions
- Other: Placebo
- Registration Number
- NCT00006401
- Lead Sponsor
- University of Colorado, Denver
- Brief Summary
To determine whether or not inhaled nitric oxide (iNO) safely decreases the incidence of chronic lung disease (CLD) in premature infants.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 793
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Inhaled Nitric Oxide (iNO) 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.
- Primary Outcome Measures
Name Time Method Participant's survival without CLD (measured at 36 weeks after birth)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (14)
Univeristy of Southern California/Good Samaritan Hospital
🇺🇸Los Angeles, California, United States
University of Iowa Hospital & Clinics
🇺🇸Iowa City, Iowa, United States
University of North Carolina Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Magee-Women's Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
Children's Hospital of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital
🇺🇸Denver, Colorado, United States
St. Joseph's Hospital
🇺🇸Phoenix, Arizona, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States