CPAP vs.Unsynchronized NIPPV at Equal Mean Airway Pressure

Study Overview
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Brief Summary
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This study seeks to determine if standard continuous positive airway pressure, known as CPAP is as effective as a more complicated approach that generates intermittent increases in airway pressure applied to the nostrils via a breathing machine. The latter is known as NIPPV and requires costly equipment to operate. Previous studies did not ensure that the average pressure applied to the lungs was equal and thus did not make for a fair comparison. The investigators believe that when the same average pressure is applied with the two techniques, CPAP is just as effective as NIPPV and may have fewer side effects, such as blowing air into the stomach. Each baby will receive CPAP or NIPPV in a random sequence for a period of 12 hours, followed by 12 hours on the alternate technique.

Detailed Description
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This is a pilot clinical trial to evaluate the comparative effectiveness of two commonly used types of non-invasive respiratory support. Preterm infants < 34 weeks gestational age, who are stable on either of the two modalities of support will be studied in a cross-over study design, such that each subject acts as his/her own control. The study will assess the relative efficacy of these modalities when used with equal mean airway pressure comparing measures of oxygenation, CO2 removal, apnea/bradycardia/desaturation events and work of breathing. The initial phase of the study is complete and preliminary analysis supports the hypothesis that there is no difference between the modalities when the mean airway pressure is equal. However we recognized that use of the RAM cannula, which does not transmit pressure effectively is an important study limitation. The findings are valid, but may only be applicable to this interface, which is widely used, but increasingly recognized as flawed. We are now extending the study to determine if the findings will be the same when short bi-nasal prongs are used.

Official Title
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Nasal Intermittent Positive Pressure Ventilation vs. Nasal Continuous Positive Airway Pressure at Equivalent Mean Airway Pressure in Preterm Infants: Effect on Oxygenation, CO2 Elimination, Work of Breathing and Frequency of Cardio-respiratory Events.

Conditions
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Prematurity, Respiratory Distress Syndrome, Apnea of Prematurity

Intervention / Treatment
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* Other: continuous positive airway pressure
* Other: nasal intermittent positive pressure ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational Age 23-34 completed weeks Stable on non- invasive respiratory support for at least 24h CPAP level of 7-12 cmH2O or NIPPV with MAP 7-12 cmH2O FiO2 requirement of <0.40 Exclusion Criteria: Clinical instability as judged by the clinical team FiO2 requirement of > 0.40 for more than 60 min. >10 apnea/bradycardia/desaturation events in past 24 h requiring moderate or vigorous stimulation. Anticipated intubation within next 24 h. Active abdominal pathology (Spontaneous Intestinal Perforation, confirmed or suspected Necrotizing Enterocolitis, bowel obstruction). Hemodynamically significant patent ductus arteriosus (PDA) Anticipated weaning off non-invasive support in the next 24 h. Any major congenital anomalies, congenital heart disease (other than PDA, atrial septal defect or ventricular septal defect) and cardiac arrhythmias Lack of study equipment or personnel Lack of parental consent

Ages Eligible for Study
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Maximum Age: 6 Months

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: Crossover Assignment
Interventional Model Description: Crossover non-inferiority trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CPAP first<br>The intervention is application of continuous positive airway pressure (CPAP). The order of the two interventions of this crossover study is randomized but each subject will be exposed to both interventions. The period of CPAP will be compared to the period of NIPPV. | Other: continuous positive airway pressure<br>* Continuous positive airway pressure is applied for 12 hours at a mean airway pressure that is the same as the subject was receiving prior to entry into the study<br>* Other names: CPAP;Other: nasal intermittent positive pressure ventilation<br>* NIPPV is applied for 12 hours at a mean airway pressure that is the same as the subject was receiving prior to entry into the study<br>* Other names: NIPPV;|
| Active Comparator: NIPPV first<br>The intervention is application of nasal intermittent positive pressure ventilation (NIPPV). The order of the two interventions of this crossover study is randomized but each subject will be exposed to both interventions. The period of CPAP will be compared to the period of NIPPV. | Other: continuous positive airway pressure<br>* Continuous positive airway pressure is applied for 12 hours at a mean airway pressure that is the same as the subject was receiving prior to entry into the study<br>* Other names: CPAP;Other: nasal intermittent positive pressure ventilation<br>* NIPPV is applied for 12 hours at a mean airway pressure that is the same as the subject was receiving prior to entry into the study<br>* Other names: NIPPV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Apnea/bradycardia events | Number of episodes of apnea and/or bradycardia that trigger alarm on the bedside monitor | Duration of intervention (12 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of of desaturation events | Number of episodes of pulse oximetry readings that trigger alarm on the bedside monitor | Duration of intervention (12 hours) | 
| Mean oxygen saturation by pulse oximetry and proportion of time below 88% | Mean oxygen saturation by pulse oximetry and proportion of time at saturation <88% | Duration of intervention (12 hours) | 
| Mean transcutaneous PCO2 and proportion of time >55 torr | Mean transcutaneous PCO2 and proportion of time at PCO2 > 55 torr | Duration of intervention (12 hours) | 
| Mean fraction of inspired oxygen | Mean fraction of inspired oxygen (FIO2) | Duration of intervention (12 hours) | 
| Mean respiratory rate | Mean respiratory rate | Duration of intervention (12 hours) | 
| Mean degrees of phase lag by RIP | Estimate of work of breathing based on phase angle as determined by respiratory inductive plethysmography | Duration of intervention (12 hours) | 
| Number of episodes of feeding intolerance | number of instances of interruption of feeding, abdominal radiographs | Duration of intervention (12 hours) | 
| Instances of treatment failure | Inability to tolerate assigned treatment by pre-defined criteria | Duration of intervention (12 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Continuous positive airway pressure, Nasal intermittent positive pressure ventilation, Mean airway pressure, Apnea, Bradycardia, Prematurity