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Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia

Phase 1
Terminated
Conditions
Pulmonary Hypertension
Bronchopulmonary Dysplasia
Interventions
Drug: inhaled nitric oxide
Drug: Placebo
Registration Number
NCT03576885
Lead Sponsor
AdventHealth
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
32
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment group - activeinhaled nitric oxideinhaled nitric oxide treatment will start at 20 ppm and continue for 2 weeks or until resolution of pulmonary hypertension, whichever comes first.
Treatment group - placeboPlaceboPlacebo treatment will start at 20 ppm and continue for 2 weeks or until resolution of pulmonary hypertension, whichever comes first.
Primary Outcome Measures
NameTimeMethod
Death36 weeks post menstrual age

Incidence of death

Bronchopulmonary (BPD) Dysplasia (Yes/no)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

Secondary Outcome Measures
NameTimeMethod
Pulmonary HypertensionDuration of treatment or up to Day 14

Pulmonary arterial pressure will be evaluated every 24-48 hours after enrollment.

Trial Locations

Locations (1)

AdventHealth

🇺🇸

Orlando, Florida, United States

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