Volume Guarantee Ventilation in Preterm Infants With Frequent Episodes of Hypoxemia

Study Overview
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Brief Summary
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Preterm infants undergoing mechanical ventilation often present with respiratory instability which leads to fluctuations in ventilation and oxygenation. In conventional modes of mechanical ventilation used in these patients, the ventilator delivers breaths at a set rate and a constant peak inspiratory pressure. We have demonstrated that spontaneous episodes of hypoxemia in mechanically ventilated preterm infants are frequently triggered by a loss in end-expiratory lung volume followed by decrease in tidal volume. This is due to a reduction in respiratory system compliance and increase in airway resistance. Volume Guarantee ventilation is a mode of ventilation in which ventilator measures the exhaled tidal volume of each ventilator breath and automatically adjusts the peak inspiratory pressure to deliver the set tidal volume. We have previously shown that Volume Guarantee reduced the severity and duration of hypoxemia episodes during a period of 2 hours in preterm infants The study hypothesis is that Volume Guarantee ventilation will decrease the duration of episodes of hypoxemia when compared to conventional mechanical ventilation during routine clinical conditions and over longer periods of time. The objective of the study is to evaluate the effects of Volume Guarantee on the duration, severity and frequency of episodes of hypoxemia in mechanically ventilated preterm infants who present with frequent hypoxemia episodes in comparison to conventional ventilation over two periods of 24 hours each and under routine clinical conditions.

Official Title
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Volume Guarantee Ventilation in Preterm Infants With Frequent Episodes of Hypoxemia

Conditions
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Episodic Hypoxemia in Mechanically Ventilated Preterm Infants

Intervention / Treatment
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* Device: Sequence A: Conventional-Volume Guarantee
* Device: Sequence B: Volume Guarantee-Conventional


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born at less than 32 weeks of gestational age. Requiring mechanical ventilation on a mandatory ventilator rate greater than or equal to 20 per minute and receiving a mean tidal volume of at least 4 ml/kg. Presenting with 4 or more episodes of hypoxemia, defined as oxygen saturation less than 75%, in the 8 hours prior to the study. Exclusion Criteria: Major congenital anomalies. Hemodynamic instability requiring inotropes within 72 hours prior to the study Culture proven sepsis within 72 hours prior to the study. Diagnosis of pulmonary interstitial emphysema or pneumothorax within the 72 hours prior to the study.
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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sequence A: Conventional-Volume Guarantee<br>This is a crossover study. Infants will be assigned to one of two sequences. Sequence A consists of a 24-hour period during which the infant receives conventional mechanical ventilation followed by a second 24 hour period during which the infant receives volume guarantee ventilation. | Device: Sequence A: Conventional-Volume Guarantee<br>* This is a crossover study. Infants will be randomly assigned to one of two sequences. In sequence A, the infant will undergo a 24-hour period of conventional mechanical ventilation followed by a 24 hour period of volume guarantee ventilation. Both conventional mechanical ventilation and volume guarantee ventilation will be provided by the same neonatal ventilator (AVEA, CareFusion Inc, Yorba Linda, CA). During the 24 hour period of conventional mechanical ventilation, the infant will receive mechanical ventilation with the settings determined by the clinical team. During volume guarantee ventilation, the set tidal volume to be maintained by the ventilator will be the average tidal volume delivered by the ventilator prior to start of study.<br>|
| Active Comparator: Sequence B: Volume Guarantee-Conventional<br>This is a crossover study. Infants will be assigned to one of two sequences. Sequence B consists of a 24-hour period during which the infant receives volume guarantee ventilation followed by a second 24 hour period during which the infant receives conventional mechanical ventilation. | Device: Sequence B: Volume Guarantee-Conventional<br>* This is a crossover study. Infants will be randomly assigned to one of two sequences. In sequence B, the infant will undergo a 24-hour period of volume guarantee ventilation followed by a 24 hour period of conventional mechanical ventilation. Both conventional mechanical ventilation and volume guarantee ventilation will be provided by the same neonatal ventilator (AVEA, CareFusion Inc, Yorba Linda, CA). During the 24 hour period of conventional mechanical ventilation, the infant will receive mechanical ventilation with the settings determined by the clinical team. During volume guarantee ventilation, the set tidal volume to be maintained by the ventilator will be the average tidal volume delivered by the ventilator prior to start of study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Time Spent With Arterial Oxygen Saturation < 75% | Percentage of time spent with arterial oxygen saturation < 75% | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Severe Hypoxemia Episodes | Frequency of severe hypoxemia episodes defined as periods with arterial oxygen saturation SpO2 < 75% lasting for at least 20 seconds. | 24 hours | 
| Frequency of Hypoxemia Episodes | Frequency of hypoxemia episodes defined as episodes with arterial saturation < 85% for at least 20 seconds | 24 hours | 
| Duration of Hypoxemia Episodes | Duration of hypoxemia episodes of arterial saturation < 85% for at least 20 seconds. Calculated as the mean episode duration per subject per period. Reported as median and inter-quartile range of all subjects. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoxemia, desaturation, mechanical ventilation, preterm infants, volume guarantee ventilation