Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia

AdventHealth

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Bronchopulmonary Dysplasia; Pulmonary Hypertension

Treatments: Drug: Placebo; Drug: inhaled nitric oxide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03576885

1170748

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 23 to 29 weeks old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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32 participants in 3 patient groups, including a placebo group

Treatment group - active

Active Comparator group

Description:

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

Treatment:

Drug: inhaled nitric oxide

Treatment group - placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Control group

No Intervention group

Description:

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