Optimising Neonatal Ventilation With Closed-loop Oxygen Control

Study Overview
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Brief Summary
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Ventilated newborns frequently need supplemental oxygen but its use must be monitored carefully as both giving too much or too little oxygen can have harmful effects. Giving too little oxygen results to low oxygen levels (hypoxia) and increases the risk of complications and mortality. Excessive oxygen delivery (hyperoxia) increases the risk of diseases involving several organs such as the retinas and the lungs. Although infants born very preterm require support with their breathing more often, more mature neonates may also need to be ventilated at birth and to receive supplemental oxygen. Therefore, they may suffer from problems related to hypoxia and hyperoxia. For the above reasons, oxygen levels are continuously monitored and the amount of oxygen provided is manually adjusted by the nurses and doctors. Closed-loop automated oxygen control systems (CLAC) are a more recent approach that involves the use of a computer software added to the ventilator. This software allows for automatic adjustment of the amount of oxygen provided to the baby in order to maintain oxygen levels within a desired target range depending on the baby's age and clinical condition. Previous studies in preterm and very small infants showed that automated oxygen control systems provided the right amount of oxygen for most of the time and prevented hypoxia and hyperoxia with fewer manual adjustments required by clinical staff. Preliminary results from a study that included infants born at 34 weeks gestation and beyond showed that CLAC systems allowed to reduce the amount of supplementary oxygen more rapidly. With this study we aim to compare the time spent in hyperoxia and the overall duration of oxygen treatment between infants whose oxygen is adjusted either manually or automatically while they remain ventilated. This will help us understand if CLAC systems help reduce the complications related to oxygen treatment.

Detailed Description
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This will be a randomised controlled trial. The investigators aim to recruit a minimum of forty ventilated infants born at or above 34 weeks of gestation. Participants will be randomised to either closed-loop automated oxygen control or manually controlled oxygen from recruitment to successful extubation. Informed written consent will be requested from the parents or legal guardians of the infants and the attending neonatal consultant will be requested to assent to the study. Eligible infants whose parents consent to the study will be enrolled within 24 hours of initiation of mechanical ventilation. Randomisation will be performed using an online randomisation generator. Patients will be ventilated using SLE6000 ventilators. Ventilator settings will be manually adjusted by the clinical team as per unit's protocol. The intervention group, in addition to standard care will also be connected to the Oxygenie closed-loop oxygen saturation monitoring software (SLE). This software uses oxygen saturations from the SpO2 probe attached to the neonate, fed into an algorithm, to automatically adjust the percentage of inspired oxygen to maintain oxygen saturations within the target range. Manual adjustments to the inspired oxygen concentration will be allowed at any point during the study if deemed appropriate by the clinical team. Patient will be studied from enrolment till successful extubation. If an infant fails extubation and required reintubation within 48 hours, he will be studied in his initial study arm. Therefore, for the infants randomised at the intervention group CLAC will resume.

Official Title
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Does Closed-loop Automated Oxygen Control During Mechanical Ventilation Reduce the Duration of Supplementary Oxygen Treatment and the Amount of Time Spent in Hyperoxia? A Randomised Trial in Ventilated Infants Born at or Near Term

Conditions
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Infant, Newborn, Diseases, Mechanical Ventilation Complication

Intervention / Treatment
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* Device: Closed-loop automated oxygen control (Oxygenie, SLE6000)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants born at or above 34 weeks completed gestation requiring mechanical ventilation and admitted to King's NICU within 24 hours of initiation of mechanical ventilation. Exclusion Criteria: Preterm infants less than 34 weeks gestation Infants with cyanotic congenital heart disease Infants on high frequency oscillatory ventilation (HFOV)
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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participating infants will be randomised either to manual oxygen control or closed-loop automated oxygen control, adjusted by clinical staff as necessary.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Manual oxygen control<br>Standard ventilation with inspired oxygen concentration adjusted manually as per unit's protocol. | |
| Other: Closed-loop automated oxygen control (Oxygenie, SLE 6000)<br>Ventilation with Oxygenie software (closed-loop automated oxygen control system), adjusted by clinical staff as necessary | Device: Closed-loop automated oxygen control (Oxygenie, SLE6000)<br>* The OxyGenie closed-loop oxygen saturation monitoring software (SLE) uses oxygen saturations from the SpO2 probe attached to the neonate, fed into an algorithm, to automatically adjust the percentage of inspired oxygen to maintain oxygen saturations within the target range. Manual adjustments including the percentage of FiO2 will be allowed at any point during the study if deemed appropriate by the clinical team.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The duration of oxygen treatment | The duration of oxygen treatment will be measured in median (interquartile range) number of days of oxygen treatment for participants in each group. | Through study completion, an average of 1 year | 
| The percentage of time spent in hyperoxia | Target oxygen saturation range for our study population is 92-96%. Hyperoxia is defined as the time spent with oxygen saturation levels exceeding 96%. The time spent in hyperoxia will be calculated as a percentage of the total time of monitoring. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of time spent receiving an inspired oxygen concentration (FiO2) above 30% | The time spent with an FiO2>30% will be calculated as a percentage of the total time of monitoring. | Through study completion, an average of 1 year |