Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants

Lung Diseases Clinical Trial

Official title:

Inhaled NO for the Prevention of Chronic Lung Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006401
• Other study ID #: 99-233
• Secondary ID: U01HL064857
• Status: Completed
• Phase: Phase 3
• First received: October 12, 2000
• Last updated: October 5, 2015
• Start date: September 2000
• Est. completion date: October 2007

Study information

• Verified date: October 2015
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 793
• Est. completion date: October 2007
• Est. primary completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 1 Year

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Lung Diseases

Intervention

Drug:
• iNO
Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants

Other:
• Placebo
Inhaled Nitrogen

Locations

Country	Name	City	State
United States	University of North Carolina Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Children's Hospital	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	University of Iowa Hospital & Clinics	Iowa City	Iowa
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Univeristy of Southern California/Good Samaritan Hospital	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital of Oklahoma	Oklahoma City	Oklahoma
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital	Phoenix	Arizona
United States	Magee-Women's Hospital	Pittsburgh	Pennsylvania
United States	Utah Valley Regional Medical Center	Provo	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kinsella JP, Cutter GR, Walsh WF, Gerstmann DR, Bose CL, Hart C, Sekar KC, Auten RL, Bhutani VK, Gerdes JS, George TN, Southgate WM, Carriedo H, Couser RJ, Mammel MC, Hall DC, Pappagallo M, Sardesai S, Strain JD, Baier M, Abman SH. Early inhaled nitric ox — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participant's survival without CLD		(measured at 36 weeks after birth)	Yes