Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia

NCT ID: NCT03576885

Last Updated: 2025-01-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-15
• Study Completion Date: 2023-10-09

Brief Summary

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.

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.

Conditions

Pulmonary Hypertension; Bronchopulmonary Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

inhaled nitric oxide

Intervention Type: DRUG

inhaled nitric oxide will be administered starting at 20 ppm. Treatment will continue for 14 days or until resolution of pulmonary hypertension

Treatment group - placebo

Placebo treatment will start at 20 ppm and continue for 2 weeks or until resolution of pulmonary hypertension, whichever comes first.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo will be administered starting at 20 ppm. Treatment will continue for 14 days or until resolution of pulmonary hypertension

Control group

Enrolled infants with no evidence of pulmonary hypertension will serve as the control group for incidence of death or bronchopulmonary hypertension

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: DRUG

Placebo

placebo will be administered starting at 20 ppm. Treatment will continue for 14 days or until resolution of pulmonary hypertension

Intervention Type: DRUG

Other Intervention Names

iNO

Eligibility Criteria

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

• Minimum Eligible Age: 23 Weeks
• Maximum Eligible Age: 29 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mallinckrodt

INDUSTRY

Sponsor Role: collaborator

Thrasher Research Fund

OTHER

Sponsor Role: collaborator

AdventHealth

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hussnain Mirza, MD

Role: PRINCIPAL_INVESTIGATOR

AdventHealth

Locations

AdventHealth

Orlando, Florida, United States

Countries

United States

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1170748

Identifier Type: -

Identifier Source: org_study_id