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

Not Applicable

Not yet recruiting

• Conditions: Ventilator Lung; Mechanical Ventilation Complication; Ventilator-Induced Lung Injury; ARDS
• Interventions: Device: Open-loop ventilator; Device: Closed-loop ventilator

• Registration Number: NCT06157073
• Lead Sponsor: University of Malaya

Brief Summary

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

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.

Study Timeline

• Status Verified: 2023-11
• Study First Submitted: 2023-11-16
• Study First Submitted QC: 2023-11-27
• Last Update Submitted: 2023-11-27
• Study First Posted: 2023-12-05
• Last Update Posted: 2023-12-05
• Study Start: 2024-01-01
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

• Decision made by treating physicians to intubate and mechanically ventilate

Exclusion Criteria

1. Suspected or confirmed pregnancy.

2. Known right ventricular heart failure upon assessment for recruitment.

3. Severe metabolic acidosis upon intubation (pH <7.2 or bicarbonate <12 mmol/L)

4. Circulatory shock requiring noradrenaline more than 0.5 mcg/kg/min upon assessment for recruitment.

5. Severe or acute life-threatening asthma.

6. Patients with chest wall deformities that would affect ventilation (e.g. severe kyphoscoliosis, diaphragmatic hernia, flail chest, trauma, pectus excavatum or carinatum, ankylosing spondylitis

7. Patients with previous lobectomy or pneumonectomy.

8. Patients with pneumothorax or other condition that requires chest drainage tube.

9. Patients with body mass index > 40 kg/m2.

10. 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.

11. Participation in another interventional trial.

12. Do-not-attempt-resuscitation (DNAR) order.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Open-loop ventilator	Open-loop ventilator	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.
Closed-loop ventilator	Closed-loop ventilator	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.

Primary Outcome Measures

Name	Time	Method
Duration of ventilation within a predefined range of acceptable respiratory parameters	Every 30 seconds for 240 minutes	Duration of ventilation (in minutes) within predefined acceptable tidal volume (TV), plateau pressure, EtCO2 and SpO2

Secondary Outcome Measures

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