Nasal Intermittent Positive Pressure Ventilation in Premature Infants (NIPPV)

Study Overview
=================
Brief Summary
-----------------
The machines and oxygen used to help very premature babies breathe can have side-effects, such as bronchopulmonary dysplasia (BPD). Infants with BPD get more complications (a higher death rate, a longer time in intensive care and on assisted ventilation, more hospital readmissions in the first year of life, and more learning problems) than infants who do not develop BPD. Doctors try to remove the tube in the wind-pipe that links the baby to the breathing machine as soon as possible. However, small babies get tired, and still require help to breathe. One of the standard and common techniques to help them breathe without a tube in the wind-pipe is to use simple pressure support, nasal continuous positive airway pressure or nCPAP. This supports breathing a little, but it is often not enough to prevent the need to go back on the breathing machine. Nasal intermittent positive pressure ventilation (NIPPV) is similar to nCPAP, but also gives some breaths, or extra support, to babies through a small tube in the nose. NIPPV is safe and effective, and already in use as an alternate standard therapy. The main research question: After being weaned from the breathing machine, is NIPPV better than nCPAP in preventing BPD in premature babies weighing 999 grams or less at birth?

Detailed Description
-----------------
The immature lung of extremely low birth weight (ELBW, < 1000 g) infants is easily damaged by the placement of an endotracheal tube to deliver mechanical ventilation and oxygen. This and the total time of mechanical ventilation contributes to bronchopulmonary dysplasia (BPD). Infants with BPD have an increased risk of later death or neuro-impairment. With the increasing survival of ELBW infants in the NICU, there has been a proportionate increase in the number of infants surviving with BPD. Following invasive ventilation via an endotracheal tube (ETT), extubation to nasal Continuous Positive Airway Pressure (nCPAP)ventilation is the standard approach. Currently, 40% of infants who are extubated and given nCPAP support fail, and require re-intubation. Previous work suggests that a less invasive respiratory support such as Nasal Intermittent Positive Pressure Ventilation (NIPPV), without an endotracheal tube is less injurious to the lung. NIPPV may thereby reduce the duration of invasive ventilator support, and aid successful early extubation. We hypothesize that the use of NIPPV leads to a higher rate of survival without BPD than standard therapy with nCPAP. This randomized clinical trial is appropriately powered to compare NIPPV with nCPAP to detect effects on clinically relevant long-term outcomes, such as death and BPD at 36 weeks. This is a multi-national, randomized, open clinical trial of two different standard methods of providing non-invasive respiratory support to 1000 extremely preterm infants weighing less than 1000 grams at birth.

Official Title
-----------------
Efficacy and Safety of NIPPV to Increase Survival Without Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants

Conditions
-----------------
Respiratory Insufficiency of Prematurity

Intervention / Treatment
-----------------
* Device: nCPAP
* Device: NIPPV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Birth weight <1000 gm Gestational age <30 completed weeks Intention to manage the infant with non-invasive respiratory support (i.e. no endotracheal tube), where either: the infant is within the first 7 days of life and has never been intubated or has received less than 24 hours of total cumulative intubated respiratory support; the infant is within the first 28 days of life, has been managed with intubated respiratory support for 24 hours or more and is a candidate for extubation followed by non-invasive respiratory support. Exclusion Criteria: Considered non-viable by clinician (decision not to administer effective therapies) Life-threatening congenital abnormalities including congenital heart disease (excluding patent ductus arteriosis) Infants known to require surgical treatment Abnormalities of the upper and lower airways Neuromuscular disorders Infants who are >28 days old and continue to require mechanical ventilation with an endotracheal tube

Ages Eligible for Study
-----------------
Maximum Age: 28 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Non-invasive respiratory support via nasal intermittent positive pressure ventilation | Device: NIPPV<br>* Deliver non-invasive respiratory support via ventilator with NIPPV device<br>|
| Active Comparator: B<br>Non-invasive respiratory support via nasal Continuous Positive Airway Pressure | Device: nCPAP<br>* Deliver non-invasive respiratory support via ventilator with nCPAP device<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of survival to 36 weeks gestational age, free of moderate-severe bronchopulmonary dysplasia |  | 36 weeks gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality at 36 weeks gestational age |  | 36 weeks gestational age | 
| All cause mortality before first discharge home |  | first discharge home | 
| retinopathy of prematurity |  | discharge home | 
| ultrasonographic evidence of brain injury |  | 36 weeks gestional age | 
| necrotizing enterocolitis |  | 36 weeks gestational age | 
| growth |  | discharge home | 
| time to establish full feeds |  | discharge home | 
| nosocomial infections |  | discharge home | 
| need for re-intubation |  | 36 weeks gestational age | 
| time on supplemental oxygen |  | discharge home | 
| duration of positive pressure respiratory support |  | discharge home | 
| comparison of synchronized and non-synchronized NIPPV |  | discharge home | 
| bronchopulmonary dysplasia |  | 36 weeks gestational age | 
| air leak syndromes |  | 36 weeks gestational age | 
| nasal trauma |  | discharge home | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
prematurity, respiratory insufficiency, non-invasive ventilation, bronchopulmonary dysplasia, hyaline membrane disease