Mid and Standard Frequency Ventilation in Infants With Respiratory Distress Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine, in preterm infants less than 37 weeks gestation with respiratory distress who are ventilated in the first 48 hours after birth, if mid frequency ventilation strategy using ventilator rate of ≥ 60 to ≤ 150 per minute compared with standard frequency ventilation strategy using ventilator rates of ≥ 20 to < 60 per minute will increase the number of alive ventilator-free days after randomization and reduce the risk of ventilator induced lung injury.

Detailed Description
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In preterm infants with respiratory distress syndrome (RDS) who are ventilated in the first 48 hours after birth, mid frequency ventilation (MFV) strategy, compared with standard frequency ventilation (SFV) strategy, in the first week after birth, will increase the number of days alive and ventilator-free in the 28 days after birth. This will be a randomized controlled trial with a 1:1 parallel allocation of infants to MFV or SFV using stratified permuted block design. Randomization will be stratified by gestational age (≥ 23 weeks to ˂ 26 weeks, ≥ 26 weeks to ≤ 28+6/7 (less than 29 weeks), and 29+0/7 to 36+6/7). Randomization of twins and higher orders (when eligible) will be to the same group. Inborn and outborn infants who are receiving assisted ventilation for RDS in the first 48 hours after birth will be included in this study. Infants with any of the following: a major malformation, a neuromuscular condition that affects respiration, terminal illness or decision to withhold or limit support will not be eligible. Infants will be randomized to MFV versus SFV. MFV delivered at rates > 60 per minute and ≤ 150 per minute, with patient triggered ventilation and pressure support. SFV delivered at rates < 60 per minute and ≥ 20 per minute, with patient triggered ventilation and pressure support.

Official Title
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A Randomized Controlled Trial of Mid and Standard Frequency Ventilation in Infants With Respiratory Distress Syndrome

Conditions
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Ventilator-Induced Lung Injury, Respiratory Distress Syndrome, Bronchopulmonary Dysplasia, Preterm Infant

Intervention / Treatment
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* Device: Mid frequency ventilation
* Device: Standard frequency ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants ≥ 23+0/7 weeks and ≤ 36+6/7 who are intubated and mechanically ventilated for respiratory distress syndrome (defined by use of surfactant) within 48 hours after birth Infants whose parents/legal guardians have provided consent for enrollment Inborn or outborn infants transferred to this center before 48 hours after birth Ventilator rate ≤ 80 per minute prior to enrollment Exclusion Criteria: a major malformation, a neuromuscular condition that affects respiration, or terminal illness or decision to withhold or limit support.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 3 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a randomized controlled trial with a 1:1 parallel allocation of infants to mid or standard frequency ventilation using stratified permuted block design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Mid frequency ventilation<br>Mid frequency ventilation delivered at rates > 60 per minute and ≤ 150 per minute, with patient triggered ventilation and pressure support. | Device: Mid frequency ventilation<br>* Mechanical ventilator used at rates > 60 per minute and ≤ 150 per minute, with patient triggered ventilation and pressure support.<br>|
| Other: Standard frequency ventilation<br>Standard frequency ventilation delivered at rates < 60 per minute and ≥ 20 per minute, with patient triggered ventilation and pressure support. | Device: Standard frequency ventilation<br>* Mechanical ventilator used at rates < 60 per minute and ≥ 20 per minute, with patient triggered ventilation and pressure support.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alive ventilator free days | The number of days alive and ventilator-free | Days 1-28 after birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alive at day 28 after birth | Number of infants alive | Day 28 after birth | 
| Ventilator free | Number of infants ventilator free | Day 28 after birth | 
| Bronchopulmonary dysplasia | Bronchopulmonary dysplasia in preterm infants less than 32 weeks' gestation | Measured at 36 weeks' postmenstrual age | 
| Bronchopulmonary dysplasia | Bronchopulmonary dysplasia in preterm infants less than 29 weeks' gestation | Measured at 36 weeks' postmenstrual age | 
| Air leak syndrome | Rate of pulmonary interstitial emphysema and/or pneumothorax | Day 1-28 after birth | 
| Pulmonary hemorrhage | Rate of pulmonary hemorrhage | Day 1-28 after birth | 
| Severe (grade 3-4) intracranial hemorrhage | Rate of severe (grade 3-4) intracranial hemorrhage in infants less than 29 weeks' gestation | Day 1-30 after birth | 
| Alive and continuous positive airway pressure/ventilator free | Number of days alive and ontinuous positive airway pressure/ventilator free | Day 1-28 after birth | 
| Alive and oxygen free | Number of days alive and oxygen free | Day 1-28 after birth | 
| Postnatal steroids | Rate of post natal steroids for bronchopulmonary dysplasia | Before 36 weeks' postmenstrual age | 
| Necrotizing enterocolitis | Rate of proven necrotizing enterocolitis (NEC) in infants less than 29 weeks' gestation | Days 1-120 after birth | 
| Neurodevelopmental impairment | Rate of moderate to severe neurodevelopmental impairment in survivors < 27 weeks' gestation | 18 to 24 months after birth | 
| Bronchopulmonary dysplasia or death | Rate of Bronchopulmonary dysplasia or death | Day 1-120 after birth | 
| Neurodevelopmental impairment or death | Rate of Bronchopulmonary dysplasia or death | Day 1-120 after birth | 
| Bronchopulmonary dysplasia or death | Rate of moderate to severe neurodevelopmental impairment or death | 18 to 24 months after birth | 
| Necrotizing enterocolitis or death | Rate of proven necrotizing enterocolitis or death | Day 1-120 after birth | 
| Death | Death before hospital discharge | Day 1-120 after birth |