Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if late doses of Infasurf surfactant given when patients are receiving inhaled nitric oxide will interact to improve surfactant function and increase survival without BPD in treated infants.

Detailed Description
-----------------
This is a multi-center, blinded, randomized controlled clinical trial to evaluate the effects of booster doses of exogenous surfactant (Infasurf®, calfactant) in addition to inhaled nitric oxide (iNO) on the outcome of survival without bronchopulmonary dysplasia (BPD, or chronic lung disease of prematurity, characterized by chronic lung dysfunction) at 36 weeks' post-menstrual age (PMA) in extremely low gestational age (ELGAN) infants that are at high risk of the development of BPD. This multi-center trial, with a planned enrollment of 524 infants, will also enable us to evaluate for any adverse effects of late surfactant treatment on short- and long-term outcomes, as we will be collecting data on effects of dosing of late surfactant, co-morbidities of prematurity and neurodevelopmental and pulmonary outcome at 1 year and 24 months corrected age. In addition, we will collect biological specimens for evaluation of the effects of late surfactant replacement therapy (administered as described in this trial) on surfactant function and inflammatory markers.

Official Title
-----------------
Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia: A Study in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide

Conditions
-----------------
Bronchopulmonary Dysplasia

Intervention / Treatment
-----------------
* Drug: Infasurf surfactant (ONY, Inc.)
* Drug: Sham (No Treatment)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: <=28 0/7 weeks gestational age Day of life 7-14 Intubated and mechanically ventilated Plan to treat with inhaled nitric oxide Exclusion Criteria: Serious congenital malformations or chromosomal abnormalities Life expectancy <7 days from enrollment Clinically unstable Less tha 48 hours since last dose surfactant Ability to obtain 36 week primary outcome information is unlikely

Ages Eligible for Study
-----------------
Minimum Age: 7 Days
Maximum Age: 14 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Infasurf surfactant (ONY, Inc.)<br>Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. | Drug: Infasurf surfactant (ONY, Inc.)<br>* Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated.<br>* Other names: Treatment;|
| Sham Comparator: Sham (No Treatment)<br>Infants already receiving inhaled nitric oxide will receive Sham (no treatment) doses on study days 0,2,4,6, and 8. | Drug: Sham (No Treatment)<br>* Late doses of Sham (No treatment) will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated.<br>* Other names: Control;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Without BPD at 36 Weeks Post Menstrual Age. | BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction. | 36 weeks post menstrual age +/- 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Without BPD at 40 Weeks | BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction. | 40 weeks PMA +/- 1 week | 
| Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age | Evaluation of respiratory outcome through the first 12 months after birth. questionnaires were administered by phone at 3,6,9 and 12 months to determine respiratory resource use (medications, home support, and hospitalization) No Pulmonary Morbidity (NoPM) was reported for infants who had no resource use in any quarter and Persistent PM was reported for infants having resource use in 3 or 4 quarters. | 1 year | 
| Pulmonary Outcomes Through 2 Years of Age | Evaluation of pulmonary outcome at 24 months of age. Evaluation of persistent wheezing based on reported wheezing during both first and second year of life. | 2 years | 
| Percentage of Participants With Neurodevelopmental Impairment (NDI) at 2 Years. | At 24 months corrected age, children underwent neuropsychological testing with the Bayley Scales of Infant Development-Third Edition (Bayley-3), and composite cognitive, language, and motor scores were collected as well as subscale scores in receptive and expressive speech and fine and gross motor. Infants with greater than one impairment as identified by testing were classified as having neurodevelopmental impairment. | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nitric oxide, surfactant, BPD, prematurity, neonates, iNO, pulmonary outcome, neurodevelopmental outcome, Infasurf, lung function, Surfactant Dysfunction, Bronchopulmonary Dysplasia