Optimising Ventilation in Preterms With Closed-loop Oxygen Control

Study Overview
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Brief Summary
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Many premature infants require respiratory support in the newborn period. Mechanical ventilation although life-saving is linked to complications for the lungs and other organs and its duration should be kept to a minimum. The use of supplemental oxygen may also increase the risk of comorbidities such as retinopathy of prematurity. Therefore, oxygen saturation levels and the amount of inspired oxygen concentration provided should be continuously monitored. Oxygen control can be performed manually or with the use of a computer software incorporated into the ventilator that is called 'closed loop automated oxygen control'(CLAC). The software uses an algorithm that automatically adjusts the amount of inspired oxygen to maintain oxygen saturation levels in a target range. Evidence suggests that CLAC increases the time spent in the desired oxygen target range but there are no data to determine the effect on important clinical outcomes. A previous study has also demonstrated that CLAC reduces the inspired oxygen concentration more rapidly when compared to manual control. That could help infants come off the ventilator sooner. With this study we want to compare the time preterm infants spend on the ventilator when we use the software to automatically monitor their oxygen levels with those infants whose oxygen is adjusted manually by the clinical team. That could help us understand if the use of automated oxygen control reduces the duration of mechanical ventilation and subsequently the complications related to it.

Detailed Description
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This will be a randomised controlled trial. The investigators aim to recruit a minimum of seventy premature ventilated infants born at less than 31 weeks gestation. Participants will be randomised to either closed-loop automated oxygen control or manually controlled oxygen from recruitment to successful extubation. The investigators will also record basic epidemiologic parameters and associated comorbidities that may impact on the duration of mechanical ventilation. Infants with known congenital anomalies will be excluded from the study. 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 48 hours of initiation of mechanical ventilation. Randomisation will be performed using an online randomisation generator. Patients will be ventilated using SLE6000 ventilators. Ventilation settings will be manually adjusted by the clinical team as per unit's protocol. The intervention group, in addition to standard care will be also 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 including the percentage of FiO2 will be allowed at any point during the study if deemed appropriate by the clinical team. The nurse-to-patient ratio will be according to the unit's protocol that is determined on the patient's acuity. Patients will be studied from enrolment until successful extubation. If an infant fails extubation and requires reintubation within 48 hours, he will be studied in his initial arm if less than 28 days old. Therefore, for those infants randomised at the intervention group CLAC will resume. Preterm infants that remain ventilated beyond day 28 of life will continue at their study arm (closed-loop automated oxygen control or manual oxygen control) till their first extubation attempt.

Official Title
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Does Closed-loop Automated Oxygen Control Reduce the Duration of Mechanical Ventilation? A Randomised Controlled Trial in Ventilated Preterm Infants

Conditions
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Infant, Premature, Diseases, Airway Morbidity, Mechanical Ventilation Complication

Intervention / Treatment
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* Device: Closed-loop automated oxygen control (Oxygenie, SLE 6000)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants less than 31 weeks completed gestation at birth requiring mechanical ventilation and admitted to King's NICU in the first 48 hours after birth Exclusion Criteria: Preterm infants above 31 weeks completed gestation or term born infants Infants with major congenital abnormalities
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<br>Ventilation with Oxygenie software (closed-loop automated oxygen control system), adjusted by clinical staff as necessary | Device: Closed-loop automated oxygen control (Oxygenie, SLE 6000)<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 mechanical ventilation | The duration of mechanical ventilation will be measured in median (interquartile range) number of days of ventilation for participants in each group. | Through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of time spent within target oxygen saturation range. | Target oxygen saturation range for our preterm population is 90-95% as per local guideline. The time spent in target range will be calculated as a percentage of the total time of monitoring. | Through study completion, an average of 2 years | 
| Number of manual adjustments to the inspired oxygen concentration required by clinical staff. | The number of manual adjustment will be calculated by reviewing the infant's medical records. | Through study completion, an average of 2 years | 
| Number of days on oxygen. | The number of days each participant will require supplementary oxygen to maintain oxygen saturation levels within target range. | Through study completion, an average of 2 years | 
| Length of Intensive Care stay | The days each participant is admitted at the Neonatal Intensive Care | Through study completion, an average of 2 years | 
| A diagnosis of bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age | The diagnosis of BPD will be calculated by reviewing the infant's medical records and respiratory status. | Through study completion, an average of 2 years |