Clinical trial NCT03576885: Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia
Official title: Treatment of Delayed Pulmonary Transition in Extremely Preterm Infants & Bronchopulmonary Dysplasia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Pulmonary Hypertension
Bronchopulmonary Dysplasia
Lead sponsor: AdventHealth
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
name: Thrasher Research Fund
First posted: 2018-07-03
Enrollment: 32
Sex: ALL
Minimum age (years): 23
Maximum age (years): 29
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Masked randomized controlled trial
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Death
timeFrame: 36 weeks post menstrual age
measure: Bronchopulmonary (BPD) Dysplasia (Yes/no)
timeFrame: 36 weeks post menstrual age
Secondary outcomes:
measure: Pulmonary Hypertension
timeFrame: Duration of treatment or up to Day 14
Other outcomes:
Locations:
city: Orlando
country: United States
facility: AdventHealth
state: Florida
Study officials:
affiliation: AdventHealth
name: Hussnain Mirza, MD
role: PRINCIPAL_INVESTIGATOR
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