Pilot Study of Topical Steroid for Prevention of Chronic Lung Disease in Extremely Premature Infants.

Study Overview
=================
Brief Summary
-----------------
A Pilot study to evaluate the safety and the efficacy of endotracheal instillation of pulmonary surfactant, with or without topical steroid (Budesonide), as a prophylactic treatment for Bronchopulmonary Dysplasia (a form of chronic lung disease) in extremely low birth weight infants. Cytokines (a group of inflammatory mediators) are measured in the tracheal aspirate before and after instillation of the study drugs.

Detailed Description
-----------------
Bronchopulmonary Dysplasia (BPD) is still one of the most common complications of ventilated premature infants. Lung inflammation plays a major role in its pathogenesis. Systemic steroids can be given to control this inflammatory process but their widespread use is limited by their systemic side effects and concerns for long neurodevelopmental adverse sequelae. Delivering steroids by inhalation which has been proven to be effective in young infants with asthma has been shown to be unsatisfactory for ELBW infants with BPD. This may be due to the fact that current delivery devices do not meet the requirements of the specific anatomical and physiologic characteristics of the airways and breathing patterns in this special group of patients. A novel approach to facilitate delivery directly to the lungs, thereby avoiding systemic concerns has been demonstrated in a recent study in which budesonide ( a topical steroid) was given to ventilated preterm infants using surfactant as a vehicle.

Official Title
-----------------
The Effect of Endotracheal Instillation of Surfactant With and Without Budesonide on the Development of Bronchopulmonary Dysplasia in Ventilator-dependent, Extremely Low Birth Weight Infants: A Pilot Study

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

Intervention / Treatment
-----------------
* Drug: Infasurf
* Drug: Pulmicort
* Other: Sham


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Birth weight 501-1000 g and ≤ 28 weeks gestational age Diagnosed as RDS requiring mechanical ventilation and surfactant therapy during the first 4 hours after birth Still ventilated on day 5-9 of life. An interval of at least 24 hours' duration between the last dose of indomethacin and the endotracheal instillation of study drug. Exclusion Criteria: Congenital or chromosomal anomalies Occurrence of perinatal sepsis Use of intravenous steroids > 7 days

Ages Eligible for Study
-----------------
Minimum Age: 24 Weeks
Maximum Age: 28 Weeks

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 |
| --- | --- |
| Experimental: A (two study drugs group)<br>The standard management + two study drugs (endotracheal instillation of a mixture containing budesonide and Infasurf) | Drug: Infasurf<br>* Endotracheal instillation of Infasurf once per week for three weeks<br>* Other names: Calfactant;Drug: Pulmicort<br>* Endotracheal instillation, once per week for three weeks<br>* Other names: Budesonide;|
| Active Comparator: B (one study drug group)<br>The standard management + one study drug (endotracheal instillation of Infasurf only). | Drug: Infasurf<br>* Endotracheal instillation of Infasurf once per week for three weeks<br>* Other names: Calfactant;|
| Sham Comparator: C (no study drug group)<br>The standard management only. | Other: Sham<br>* None instilled through the endotracheal tube<br>* Other names: Air Sham;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the effect of surfactant with and without Budesonide on the development of BPD in ELBW infants. | The main goal of the study is to determine whether endotracheal instillation of surfactant (Infasurf) with or without potent topical steroid (Budesonide) reduces the development of Bronchopulmonary Dysplasia (BPD) in Extremely Low Birth Weight (ELBW) infants at high risk of BPD. | Supplemental oxygen requirement at 36 weeks' postmenstrual age (PMA) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the effect of surfactant with and without Budesonide on the inflammatory cytokines in tracheal aspirates. | Tracheal aspirate samples will be collected before instillation of each dose of the study drug, 7 days after the last dose if the infant is still intubated, and prior to elective extubation regardless of when extubation occurs. Tracheal aspirate samples will be obtained from the control (standard management) group in the same way and using the same time frame as the treatment groups | The measurement of cytokines in tracheal aspirate samples will be done at the end of the study. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bronchopulmonary Dysplasia, Budesonide, Infasurf