Efficacy and Safety of Automated Closed-loop Ventilator vs Conventional Open-loop Ventilator in the Emergency Department

Study Overview
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Brief Summary
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Patients presenting to the emergency department (ED) may require breathing support with machines depending on the condition. Throughout the breathing support, the settings on the breathing machines will be tailored to the patient's requirements. These settings are manually adjusted by trained physicians. Currently, there are machines which can automatically change the settings based on real-time specific information obtained from the patient. This study aims to compare the use of machines which require manual adjustments (open-loop conventional ventilators) and machines which can automatically change the settings (closed-loop automated ventilators). Patients will be carefully selected to ensure no harm is caused whilst delivering the best care. This study will look into the duration when patients are receiving optimum settings and levels of oxygen and carbon dioxide in the blood. The outcomes of this study would allow us to identify methods to improve patient care.

Detailed Description
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Invasive mechanical ventilation is a lifesaving intervention for patients with respiratory failure in the emergency department (ED). Recent technological advancements have introduced closed-loop automated ventilators as a potential alternative to open-loop conventional ventilators. However, the efficacy and safety of closed-loop automated ventilators in the emergency setting remains understudied. This research aims to evaluate the efficacy and safety of closed-loop automated ventilator compared to open-loop conventional ventilator in intubated and ventilated patients in the ED. A randomized controlled trial will be conducted in an ED of a tertiary university-affiliated hospital. Eligible patients are 18 years or older, decision made by treating physicians to intubate and mechanically ventilate. Some of exclusion criteria are pregnancy, heart failure, metabolic acidosis, circulatory shock, life-threatening asthma and morbid obesity. The primary measure of efficacy is the duration of ventilation within a predefined range of acceptable respiratory parameters between automated and conventional ventilation. Secondary outcome measures are; number of manual adjustments required to attain targeted settings in automated and conventional ventilators, PaO2/FiO2 ratio (PF ratio), arterial blood gas results, vital signs, breath-by-breath analysis, and rate of ventilator dyssynchrony. The ventilator used in the intervention arm is the closed-loop automated ventilator Hamilton C6s INTELLIVENT-ASV (Hamilton Medical AG, Switzerland). Hamilton C1 ASV is chosen as the open-loop conventional comparator as it is similar to Hamilton C6s INTELLIVENT-ASV, without the INTELLIVENT software. Based on Lellouche et al, the calculated total sample size with a dropout rate of 10% is 132. The data is analysed based on the intention-to-treat (ITT) and per-protocol (PP) principles. The primary endpoint measurements are reported as areas under the curves (AUC) within the predefined range of acceptable respiratory parameters. Between-group differences in continuous variables are analysed using independent t-test or Mann-Whitney U test. Between-group differences in categorical variables are analysed using chi-square test.

Official Title
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A Randomized, Controlled Trial to Evaluate the Efficacy and Safety of Fully Automated Closed-loop Ventilator Versus Conventional Open-loop Ventilator in Ventilated Patients in the Emergency Department

Conditions
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Ventilator Lung, Mechanical Ventilation Complication, Ventilator-Induced Lung Injury, ARDS

Intervention / Treatment
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* Device: Closed-loop ventilator
* Device: Open-loop ventilator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Decision made by treating physicians to intubate and mechanically ventilate Exclusion Criteria: Suspected or confirmed pregnancy. Known right ventricular heart failure upon assessment for recruitment. Severe metabolic acidosis upon intubation (pH <7.2 or bicarbonate <12 mmol/L) Circulatory shock requiring noradrenaline more than 0.5 mcg/kg/min upon assessment for recruitment. Severe or acute life-threatening asthma. Patients with chest wall deformities that would affect ventilation (e.g. severe kyphoscoliosis, diaphragmatic hernia, flail chest, trauma, pectus excavatum or carinatum, ankylosing spondylitis Patients with previous lobectomy or pneumonectomy. Patients with pneumothorax or other condition that requires chest drainage tube. Patients with body mass index > 40 kg/m2. Manufacturer's contraindications: Difference in oxygen saturation between pulse oximetry (SpO2) and arterial sample (SaO2) of more than 5% (due to unreliable sensor). Difference in carbon dioxide level between end-tidal sensor (ETCO2) and arterial sample (PaCO2) of more than 5 mm Hg (due to unreliable sensor). Known pneumothorax and bronchopulmonary fistula upon assessment for recruitment. Participation in another interventional trial. Do-not-attempt-resuscitation (DNAR) order.

Ages Eligible for Study
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Minimum Age: 18 Years

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects who meet all criteria for enrolment will be randomized in a 1:1 allocation ratio to receive either open-loop ventilator (OLV) or closed-loop ventilator (CLV). Randomization will be stratified by the respiratory pathology present: normal lung, hypercapnic respiratory failure and decreased lung compliance. Randomization sequence will be generated using a web-based randomisation software.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Open-loop ventilator<br>Prior to the rapid sequence intubation, patients' gender and height are set on the ventilator. The physician in-charge will setup the ventilator based on the lung condition, following the research protocol. Patients will be connected to this ventilator upon securing the airway. Ventilator setting parameters will be manually adjusted by the in-charge physician following local guidelines. | Device: Open-loop ventilator<br>* Conventional closed-loop ventilator with manual adjustments by the physician in charge<br>|
| Experimental: Closed-loop ventilator<br>Prior to the rapid sequence intubation, patients' gender and height are set on the ventilator. Patients' condition settings are selected depending on the lung condition. The sensors for end-tidal carbon dioxide (EtCO2) and oxygen saturation (SpO2) will be connected. Patients will be connected to this ventilator upon securing the airway. Ventilator setting parameters will be set following the study protocol. | Device: Closed-loop ventilator<br>* Fully automated closed-loop ventilator using the INTELLIVENT software<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of ventilation within a predefined range of acceptable respiratory parameters | Duration of ventilation (in minutes) within predefined acceptable tidal volume (TV), plateau pressure, EtCO2 and SpO2 | Every 30 seconds for 240 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Manual adjustments of ventilator settings | Frequency of manual adjustments of ventilator settings and the parameters requiring adjustments | Any time the manual adjustment is performed throughout the 4-hour study period | 
| Physiological data - blood pressure | Patient's blood pressure in mmHg | Mean hourly for 4 hours | 
| Physiological data - respiratory rate | Patient's respiratory rate in breaths per minute | Mean hourly for 4 hours | 
| Physiological data - heart rate | Patient's heart rate in beats per minute | Mean hourly for 4 hours | 
| Biochemical data - pH | Arterial pH levels | Upon intubation, at 1-hour, 2-hour, 3-hour and 4-hour | 
| Biochemical data - CO2 and O2 | Arterial partial pressure of carbon dioxide and oxygen in mmHg | Upon intubation, at 1-hour, 2-hour, 3-hour and 4-hour | 
| Biochemical data - bicarbonate | Arterial bicarbonate levels in mmol/L | Upon intubation, at 1-hour, 2-hour, 3-hour and 4-hour | 
| Patient outcome - mechanical ventilation | Duration of mechanical ventilation | Assessed from time of intubation to time of successful extubation or death from any cause, whichever came first, assessed up to 28 days | 
| Patient outcome - LOS ED | Length of stay in emergency department | Assessed from time of triage to time patient leaves ED or death, whichever comes first, up to 7 days | 
| Patient outcome - LOS ICU | Length of intensive care unit stay | Assessed from time of admission into the ICU to time of transfer to general ward or death, whichever comes first up to 28 days | 
| Patient outcome - LOS hospital | Length of hospital stay | Assessed from time of triage in ED to time of discharge or in-hospital death, whichever comes first up to 28 days | 
| Mortality rate | Number and percentage of deaths | At 14 and 28 days after recruitment | 
| Number of patients developing ARDS and pneumothorax | Development of complications (pneumothorax, ARDS) during study and throughout admission | At anytime within the 4-hour intervention or upon discharge or diagnosis of complications | 
| Ventilator data - airway pressures | Ventilator parameters: mean and peak airway pressures in cmH20 | Every 30 seconds for 240 minutes | 
| Ventilator data - FiO2 | Ventilator parameters: fraction of inspired oxygen (FiO2) | Every 30 seconds for 240 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mechanical ventilation, closed loop ventilator, open loop ventilator, emergency department