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”

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

This trial will be a multi-center, double blind, placebo-controlled, randomized clinical trial. All infants < 30 weeks GA at birth will be screened for enrollment. Infants who require mechanical ventilation or positive pressure support at any point during days 5 to 14 after birth will be randomized to iNO starting at 20 ppm, or matched placebo, by means of a blinded INOvent® delivery device. Randomization will be stratified by center and gestational age (< 27 weeks GA and 27 to 30 weeks GA), and treatment will be assigned using an interactive voice or web-based response system. 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 postmenstrual age (PMA) using a physiologic assessment of BPD.

Intervention(s) in this Clinical Trial

• Drug: Inhaled Nitric Oxide
  • Inhaled Nitric Oxide will be administered continuously starting at 20ppm into the inspiratory limb of the ventilator circuit in mechanically ventilated subject using an INOvent delivery system of by nasal cannula as needed for 24 days of therapy.
• Drug: Placebo
  • Nitrogen gas will be administered in the same manner as the experimental drug.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Inhaled Nitric Oxide
  • Inhaled Nitric Oxide
• Placebo Comparator: Placebo
  • Nitrogen Placebo

Primary Measures

• Arterial Blood Gases
  • Time Frame: Baseline, 36 weeks PMA, at discharge
    Safety Issue?: No

Secondary Measures

• Vital Signs
  • Time Frame: Baseline, 1 hour, day 1, weeks 36, 40, 44 PMA, at discharge
    Safety Issue?: No
• Methemoglobin levels
  • Time Frame: Baseline, days 1 through 3
    Safety Issue?: Yes
• cGMP levels
  • Time Frame: Baseline, days 3 through 24, 36 weeks PMA
    Safety Issue?: No
• Adverse Events
  • Time Frame: Treatment duration
    Safety Issue?: Yes
• Serious Adverse Events
  • Time Frame: Study duration
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 14 Days

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: INO Therapeutics Industry

Overall Clinical Trial Officials and Contacts

James Baldassarre, MD Study Director INO Therapeutics  

Overall Contact: Karen Kelly 908-238-6387 karen.kelly@ikaria.com

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00931632

Study ID Number: IK-3001-BPD-301

ClinicalTrials.gov Identifier: NCT00931632

Health Authority: United States: Food and Drug Administration