Clinical trial NCT00931632: Inhaled Nitric Oxide (INO) for the Prevention of Bronchopulmonary Dysplasia (BPD) in Preterm Infants
Official title: Inhaled Nitric Oxide (INO) for the Prevention of Bronchopulmonary Dysplasia (BPD) in Preterm Infants Requiring Mechanical Ventilation or Positive Pressure Support on Days 5-14 After Birth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bronchopulmonary Dysplasia
Keywords: Bronchopulmonary Dysplasia, BPD
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2009-07-02
Enrollment: 451
Sex: ALL
Minimum age (years): 5
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase 3, multi-center, double blind, placebo-controlled, randomized clinical trial will attempt to demonstrate if preterm infants who require mechanical ventilation and/or positive pressure support at any point during days 5 to 14 after birth may benefit from treatment with iNO.

Detailed description: Multi-center, double blind, placebo-controlled, randomized clinical trial. Infants who meet all enrollment criteria at any point during days 5 to 14 after birth will be randomized to inhaled NO starting at 20 ppm, or matching placebo, by means of a blinded INOvent® delivery device. All infants will receive 24 days of therapy, following a dose reduction schedule. Infants who are extubated before 24 days will continue therapy via nasal continuous positive airway pressure (CPAP) or nasal cannula to complete 24 days' of therapy. The primary outcome measure will be survival without BPD at 36 weeks gestational age using a physiologic assessment of BPD.

Eligibility criteria: Inclusion Criteria:

* Preterm infants who are:

  1. 500 to 1250 grams at birth
  2. \< 30 weeks gestational age
  3. 5 to 14 days of age (inclusive) at the time of entry
  4. Requiring mechanical ventilation or for those infants ≤ 800 grams, positive pressure support (including CPAP) for respiratory insufficiency on days 5 to 14 days of age (inclusive)

Exclusion Criteria:

1. Preterm infants with life-threatening anomalies (cranial, cardiac, thoracic, chromosomal) or congenital diaphragmatic hernia with lung hypoplasia, or any subject who will not receive complete intensive care
2. Preterm infants with bilateral Grade 4 intraventricular hemorrhage (IVH)
3. Subjects who are dependent on right to left shunting to maintain the systemic circulation
4. Preterm infants who received prior iNO therapy
5. Use of another investigational agent

Primary outcomes:
measure: Survival Without BPD at 36 Weeks
timeFrame: Baseline, 36 weeks PMA
Secondary outcomes:
measure: Days of Airway Pressure Support - Intent-to-treat Population
timeFrame: Through hospital discharge, an average of 105 days for placebo and 108 days for INO
measure: Length of Birth Hospitalization
timeFrame: Through hospital discharge, an average of 105 days for placebo and 108 days for INO
measure: Number and Percentage of Participants With Use of Postnatal Corticosteroids for Bronchopulmonary Dysplasia
timeFrame: Through hospital discharge, an average of 105 days for placebo and 108 days for INO
measure: Number and Percentage of Participants With Use of Postnatal Corticosteroids for Any Medical Reason
timeFrame: Through hospital discharge, an average of 105 days for placebo and 108 days for INO
measure: Systemic Use of Postnatal Corticosteroids for Any Medical Reason
timeFrame: Through hospital discharge, an average of 105 days for placebo and 108 days for INO
measure: Number of Days of Oxygen Use
timeFrame: Through hospital discharge, an average of 105 days for placebo and 108 days for INO
measure: Severity of Bronchopulmonary Dysplasia
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University School of Medicine
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital of San Diego
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women and Newborns
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Orlando
country: United States
facility: Winnie Palmer Hospital for Women and Babies
state: Florida
city: Tampa
country: United States
facility: University of So Florida College of Medicine
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Park Ridge
country: United States
facility: Advocate Lutheran General Children's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Louisville
country: United States
facility: University of Louisville School of Medicine
state: Kentucky
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Neptune City
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: The Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Valhalla
country: United States
facility: Maria Fareri Children's Hospital at Westchester Medical Center
state: New York
city: Raleigh
country: United States
facility: WakeMed Faculty Physicians, Neonatology
state: North Carolina
city: Toledo
country: United States
facility: Mercy Children's Hospital
state: Ohio
city: Tulsa
country: United States
facility: Saint Francis Children's Hospital
state: Oklahoma
city: Greenville
country: United States
facility: Greenville Memorial Hospital
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Children's Hospital
state: South Dakota
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Wheaton Franciscan Healthcare
state: Wisconsin
city: Wauwatosa
country: United States
facility: Children's Corporate Center, Division of Neonatology
state: Wisconsin
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
Study officials:
affiliation: Mallinckrodt
name: James Baldassarre, MD
role: STUDY_DIRECTOR
References:
citation: Hasan SU, Potenziano J, Konduri GG, Perez JA, Van Meurs KP, Walker MW, Yoder BA; Newborns Treated With Nitric Oxide (NEWNO) Trial Group. Effect of Inhaled Nitric Oxide on Survival Without Bronchopulmonary Dysplasia in Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2017 Nov 1;171(11):1081-1089. doi: 10.1001/jamapediatrics.2017.2618.