Clinical trial NCT00006401: Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants
Official title: Inhaled NO for the Prevention of Chronic Lung Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Diseases
Bronchopulmonary Dysplasia
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2000-10-13
Enrollment: 793
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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)

Primary outcomes:
measure: Participant's survival without CLD
timeFrame: (measured at 36 weeks after birth)
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Univeristy of Southern California/Good Samaritan Hospital
state: California
city: Denver
country: United States
facility: Children's Hospital
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Iowa City
country: United States
facility: University of Iowa Hospital & Clinics
state: Iowa
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Children's Hospital of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Women's Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Provo
country: United States
facility: Utah Valley Regional Medical Center
state: Utah
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: John P. Kinsella, MD
role: STUDY_CHAIR
References:
citation: 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 oxide therapy in premature newborns with respiratory failure. N Engl J Med. 2006 Jul 27;355(4):354-64. doi: 10.1056/NEJMoa060442.
citation: Mourani PM, Kinsella JP, Clermont G, Kong L, Perkins AM, Weissfeld L, Cutter G, Linde-Zwirble WT, Abman SH, Angus DC, Watson RS; Prolonged Outcomes after Nitric Oxide (PrONOx) Investigators. Intensive care unit readmission during childhood after preterm birth with respiratory failure. J Pediatr. 2014 Apr;164(4):749-755.e3. doi: 10.1016/j.jpeds.2013.11.062. Epub 2013 Dec 31.
citation: Watson RS, Clermont G, Kinsella JP, Kong L, Arendt RE, Cutter G, Linde-Zwirble WT, Abman SH, Angus DC; Prolonged Outcomes After Nitric Oxide Investigators. Clinical and economic effects of iNO in premature newborns with respiratory failure at 1 year. Pediatrics. 2009 Nov;124(5):1333-43. doi: 10.1542/peds.2009-0114. Epub 2009 Oct 19.