Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia

June 28, 2023 updated by: AdventHealth

Treatment of Delayed Pulmonary Transition in Extremely Preterm Infants & Bronchopulmonary Dysplasia

Inhaled nitric oxide (iNO) is an effective treatment for pulmonary hypertension (PH) in term and near-term infants. Preterm infants are at risk for early PH that is associated with high risk for bronchopulmonary dysplasia or death. In multiple clinical trials, iNO treatment was not effective for BPD prevention. However, infants were not screened for PH and iNO treatment was not targeted for PH. iNO treatment for PH in preterm infants is controversial due to lack of evidence. The study team hypothesizes that early diagnosis of PH (72-96 hours of life) and iNO treatment will decrease the incidence of death and bronchopulmonary dysplasia and improve oxygenation in extremely preterm infants.

  1. To determine if iNO treatment of extremely preterm infants with early pulmonary hypertension as established with echocardiographic evidence at 72-96 hours of age will decrease incidence of death or BPD.
  2. To determine if iNO treatment of extremely preterm infants with early PH will decrease the pulmonary artery pressure and improve oxygenation within 72 hours of intervention.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single center, blinded, randomized control clinical trial to evaluate the effects of inhaled nitric oxide on the outcome of survival and incidence of bronchopulmonary dysplasia. This trial has a planned enrollment of 138 infants with 68 infants with delayed pulmonary transition assigned to either the treatment or placebo group. There is no enrollment restriction based on gender, ethnicity, or race. Enrollment is expected to take 36 months with an additional 12 months for data analysis.Infants with early pulmonary hypertension will be randomized to the treatment or placebo group. Treatment will continue until resolution of pulmonary hypertension or through Day 14, whichever comes first. Serial echocardiograms will be performed every 48 hours +/-12 hours until Day 14. Oxygen saturation levels will be averaged every 24 hour period following enrollment. This study will provide evidence for the beneficial effects of early diagnosis and treatment of pulmonary hypertension in preterm infants.

Study Type

Interventional

Enrollment (Estimated)

138

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 months to 9 months (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Step 1:

  • Birth between 23 weeks and 0 days and 29 weeks and 6 days.
  • Positive pressure ventilation at 72-96 hours of age

Step 2:

  • Early pulmonary hypertension

Exclusion Criteria:

Step 1:

  • Death prior to 12 hours of age or first echocardiogram
  • Chromosomal anomalies
  • Major congenital anomalies
  • Myocardial dysfunction
  • Complex cardiac defect
  • Dependent on right to left shunting of blood

Step 2:

  • Excessive pulmonary blood flow (left to right shunt across PDA)
  • Pulmonary blood flow obstruction secondary to pulmonary vein stenosis
  • Mitral valve stenosis
  • Cor triata
  • Aortic valve atresia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Treatment group - active
inhaled nitric oxide treatment will start at 20 ppm and continue for 2 weeks or until resolution of pulmonary hypertension, whichever comes first.
Drug: inhaled nitric oxide
inhaled nitric oxide will be administered starting at 20 ppm. Treatment will continue for 14 days or until resolution of pulmonary hypertension
Other Names:
  • iNO
Placebo Comparator: Treatment group - placebo
Placebo treatment will start at 20 ppm and continue for 2 weeks or until resolution of pulmonary hypertension, whichever comes first.
Drug: Placebo
placebo will be administered starting at 20 ppm. Treatment will continue for 14 days or until resolution of pulmonary hypertension
No Intervention: Control group
Enrolled infants with no evidence of pulmonary hypertension will serve as the control group for incidence of death or bronchopulmonary hypertension

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death (yes/no)
Time Frame: 36 weeks post menstrual age
Incidence of death
36 weeks post menstrual age
Bronchopulmonary (BPD) dysplasia (yes/no)
Time Frame: 36 weeks post menstrual age
Incidence of bronchopulmonary dysplasia as determined by need for positive pressure ventilation or supplemental oxygen after room air challenge test
36 weeks post menstrual age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pulmonary arterial pressure (mmHg)
Time Frame: Duration of treatment or up to Day 14
Pulmonary arterial pressure will be averaged for each 24-48 hour period after enrollment
Duration of treatment or up to Day 14
Oxygen saturation level percentage
Time Frame: Duration of treatment or up to Day 14
Oxygen saturation level will be averaged for each 24 hour period after enrollment
Duration of treatment or up to Day 14
SF (SpO2/FiO2) ratio
Time Frame: Duration of treatment or up to Day 14
Pulse oximetric saturation Spo2/Fio2 ratio
Duration of treatment or up to Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AdventHealth

Collaborators

Mallinckrodt
Thrasher Research Fund

Investigators

  • Principal Investigator: Hussnain Mirza, MD, AdventHealth

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2019

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

June 22, 2018

First Submitted That Met QC Criteria

June 22, 2018

First Posted (Actual)

July 3, 2018

Study Record Updates

Last Update Posted (Actual)

June 29, 2023

Last Update Submitted That Met QC Criteria

June 28, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1170748

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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