Nasal HFOV Versus Nasal CPAP to Reduce Post-extubation pCO2

Study Overview
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Brief Summary
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To investigate whether nasal high frequency oscillation ventilation (nHFOV) immediately after extubation reduces the arterial partial pressure of carbon dioxide (paCO2) at 72 hours after extubation in comparison with nasal continuous positive airway pressure (nCPAP) in very low birth weight infants (VLBWs).

Detailed Description
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Randomized controlled clinical trial comparing nHFOV vs nCPAP immediately after extubation of VLBW infants. Intervention and treatment protocol as described for the two study arms. Definition of treatment failure (infant meets at least one criterion): Sustained pCO2 >80 mmHg and pH <7.20 confirmed by arterial or capillary blood gas analysis in spite of optimized non-invasive respiratory support with maximum settings as defined above. Fraction of inspired oxygen (FiO2) >0.6 to maintain peripheral oxygen saturation as measured by pulse oximetry (SpO2) at 90-94% in spite of optimized non-invasive respiratory support with maximum settings as defined above. Reintubation (study patients may be intubated at any time, due to clinical considerations, with or without reaching another criterion of treatment failure). Sample size: Assuming a variability of the paCO2 as previously reported for difficult-to-wean preterm infants in our unit (Czernik C, J Matern Fetal Neonatal Med 2012) and a treatment failure rate of 22% within 72 hours after extubation, we calculated a sample size of 34 patients in each study arm to detect a difference in the paCO2 of 7 mmHg, using a two-sided significance of 0.05 and a power of 0.8. Randomization: Sequence generation by an independent statistician and a study nurse. Block randomization using at least two different block sizes. Allocation concealment using sequentially numbered opaque sealed envelopes. Data monitoring: By an independent statistician.

Official Title
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Nasal High Frequency Oscillation Ventilation Versus Nasal Continuous Positive Airway Pressure to Reduce Post-extubation pCO2 in Very Low Birth Weight Infants: a Randomized Controlled Trial

Conditions
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Respiratory Distress Syndrome, Newborn, Respiratory Tract Diseases

Intervention / Treatment
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* Device: nHFOV
* Device: nCPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age <32+0 weeks Birth weight <1500 g Received mechanical ventilation via an endotracheal tube for ≥120 h Caffeine treatment according to unit guidelines paCO2 <65 mmHg with pH >7.2 FiO2 25-40% to maintain SpO2 at 90-94%. Time-cycled, pressure-controlled ventilation: PIP ≤22 cm H2O, PEEP ≤6 cm H2O; Volume guarantee ventilation: Working Ppeak ≤22 cm H2O, PEEP ≤6 cm H2O; High frequency oscillation ventilation: Pmean ≤12 cm H2O, Amplitude ≤30 cm H2O Decision of the attending clinician to extubate Exclusion Criteria: Major congenital malformation requiring surgery Duct-dependent congenital heart disease Neuromuscular disease Participation in another randomized controlled trial Death before reaching the eligibility criteria Hydrocortisone treatment at the time of enrolment Chronological age >28 days

Ages Eligible for Study
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Minimum Age: 5 Days
Maximum Age: 28 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nHFOV<br>Immediately after extubation, nHFOV is provided via binasal prongs. Ventilator settings: Frequency set at 10 Hz, I:E ratio 33:66, amplitude 20 cm H2O, Pmean 8 cm H2O, flow 7 l/min. Set FiO2 to maintain SpO2 at 90-94%. The weaning process is left to the discretion of the attending physician. Maximum amplitude 30 cm H2O, minimum frequency 9 Hz, maximum Pmean 8 cm H2O. For infants in the nHFOV-group who fail nHFOV (see definition below), but do not need immediate reintubation, a non-invasive Rescue-Treatment may be provided. The decision to attempt Rescue-Treatment, the mode of respiratory support and the ventilator settings used are at the discretion of the attending clinician. | Device: nHFOV<br>* Extubation to ventilator-derived nHFOV using binasal prongs<br>|
| Active Comparator: nCPAP<br>Immediately after extubation, nCPAP is provided via binasal prongs. Ventilator settings: CPAP level set at 8 cm H2O, flow 7 l/min. Set FiO2 to maintain SpO2 at 90-94%. The weaning process is left to the discretion of the attending physician. Maximum CPAP level 8 cm H2O, maximum flow 8 l/min. For infants in the nCPAP-group who fail nCPAP (see definition below), but do not need immediate reintubation, Rescue-nHFOV via binasal prongs may be provided. The decision to attempt Rescue-nHFOV and the ventilator settings used are at the discretion of the attending clinician. | Device: nCPAP<br>* Extubation to ventilator-derived nCPAP using binasal prongs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| paCO2 at 72 h After Extubation | Partial pressure of arterial carbon dioxide assessed between 64 and 80 hours, and on average 72 hours. | 64 h to 80 h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pH at 2 h After Extubation |  | within the first 6 h after extubation | 
| paO2 at 2 h After Extubation |  | within the first 6 h after extubation | 
| paCO2 at 2 h After Extubation |  | within the first 6 h after extubation | 
| Base Excess at 2 h After Extubation |  | within the first 6 h after extubation | 
| pH at 72 h After Extubation |  | 64-80 h after extubation | 
| paO2 at 72 h After Extubation |  | 64-80 h after extubation | 
| Base Excess at 72 h After Extubation |  | 64-80 h after extubation | 
| Successful Extubation | Defined as the number of patients breathing spontaneously in their assigned treatment group for ≥72h without reaching the criterion of treatment failure | 72 h after extubation | 
| Treatment Failure | Defined as the number of patients reaching the criterion of treatment failure | within 7 days after extubation | 
| Reintubation | Defined as the number of patients being reintubated | within 7 days after extubation | 
| Highly Viscous Secretions | Defined as the documented number of episodes of airway obstruction due to highly viscous secretions per patient | within 72 hours after extubation | 
| Other Adverse Effects | Incidences of the following adverse effects: Intraventricular hemorrhage III°-IV° (Papile), surgical necrotizing enterocolitis, pneumothorax, pulmonary interstitial emphysema, persistent ductus arteriosus requiring surgical closure, retinopathy of prematurity requiring laser treatment and/or injection of bevacizumab, death or moderate to severe bronchopulmonary dysplasia (Jobe) at 36 weeks' gestational age, periventricular leukomalacia | until discharge | 
| Duration of Respiratory Support | Total duration of mechanical ventilation, total duration of supplemental oxygen, number of infants discharged with home oxygen | until discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prematurity, High Frequency Oscillation Ventilation, Nasal Continuous Positive Airway Pressure, Airway Extubation