Study of Inhaled Nitric Oxide (iNO) and Respiratory Outcomes in Late Preterm Infants

The Use of Inhaled Nitric Oxide to Improve Respiratory Outcomes in Late Preterm Infants

The aim of this study is to determine if inhaled nitric oxide will improve short and long term respiratory outcomes in preterm infants. Infants born at a gestational age of 30-36 weeks and who require breathing support with high flow nasal cannula, nasal continuous positive airway pressure, or nasal intermittent positive pressure will be randomized to receive either inhaled nitric oxide or placebo. The dose will then be decreased per protocol until all respiratory support has been discontinued. Infants will be followed to evaluate safety and efficacy of non-invasive iNO delivery, up to 12 months corrected gestational age.

Study Overview

• Status: Terminated
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Drug: inhaled nitric oxide; Drug: Placebo Comparator - nitrogen gas

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• <48 hours of age,
• 30 - 36 weeks gestational age at birth based on best estimate using obstetrical sonography (first or second trimester), solid dating criteria, or Ballard examination,
• Birth weight of ≥ 1,000 g,
• 5 minute Apgar score ≥5,
• Requiring nasal cannula O2 > 1 liter per minute (LPM), continuous positive pressure (CPAP), or non invasive positive pressure ventilation (NIPPV) for treatment of respiratory failure,
• Requiring a fraction of inspired oxygen (FIO2) of at least 0.25 to maintain arterial oxygen saturation (SaO2) 88-94%,
• Parent or guardian has signed informed consent and agrees to all study- related procedures, including those required after hospital discharge.

Exclusion Criteria:

• Major congenital anomaly
• Intubation and surfactant in the delivery room or prior to enrollment in the Neonatal Intensive Care Unit (NICU). Excludes intubation for suctioning.
• Known congenital infection (bacterial, viral),
• Perinatal asphyxia (5 minute Apgar <5, umbilical artery pH < 7.0 or evidence of neonatal encephalopathy),
• Mother and/or infant is enrolled in another clinical trial (excluding observational) or has received an investigational drug,
• Has undergone or is anticipated to require a major surgical procedure within the first 48 h of life,
• Any condition which could preclude receiving study drug or performing any study-related procedures,
• Use of postnatal corticosteroids,
• Parent or guardian is unable or unwilling to complete study procedures after hospital discharge.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: inhaled Nitric Oxide; iNO to start at 20 parts per million (ppm) for the first three days of life. The dose will then be decreased to 10 ppm for three days, 5 ppm for 3 days and then 2 ppm until all high flow respiratory support has been discontinued.	Drug: inhaled nitric oxide; Other Names: iNO, INOmax
Placebo Comparator: Nitrogen Gas; Placebo gas will be adjusted the same as study gas: to start at 20ppm for the first three days of life. The dose will then be decreased to 10 ppm for three days, 5 ppm for 3 days and then 2 ppm until all high flow respiratory support has been discontinued.	Drug: Placebo Comparator - nitrogen gas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Were Alive Without the Need for Intubation or Mechanical Ventilation Within the First Week of Life	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Had the Need for Exogenous Surfactant		7 days
Total Length of Hospital Stay	participants who were followed for the duration of hospital stay	From hospital admission through discharge
Total Duration of Supplemental Oxygen	Participants were followed for the duration of hospital stay for use of supplemental oxygen	From Hospital Admission through discharge
Diagnosis of Bronchopulmonary Dysplasia (BPD)	Diagnosis of BPD by oxygen challenge test at 36 weeks post menstrual age (PMA) for infants born between 30 and 32 weeks gestational age (GA). For those born 32 1/7 - 36 weeks, an oxygen challenge test was performed at 1-2 months of age.	At 36 weeks postmenstrual age or 1-2month of age
Evidence of Chronic Respiratory Morbidity at 12 Months Corrected Gestational Age (CGA)	defined by a validated system of parental diaries and pulmonary questionnaires, as well as review of medical records (medical visits, respiratory medication use, emergency room visits, and hospital re-admissions)	12 months corrected gestational age
Total Duration of Respiratory Support	participants were followed for the duration of hospital stay for respiratory support	From hospital admission through discharge

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Jennifer W Lee, MD, MS, Tufts Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: December 10, 2012
• First Posted (Estimate): December 12, 2012

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: June 20, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Inhaled Nitric Oxide; Bronchopulmonary Dysplasia; Late Prematurity; Chronic Respiratory Morbidity
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: 10487 (Other Identifier: CTEP)