Clinical trial NCT06157073: Efficacy and Safety of Automated Closed-loop Ventilator vs Conventional Open-loop Ventilator in the Emergency Department
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Ventilator Lung
Mechanical Ventilation Complication
Ventilator-Induced Lung Injury
ARDS
Keywords: mechanical ventilation
closed loop ventilator
open loop ventilator
emergency department
Lead sponsor: University of Malaya
Sponsor class: OTHER
First posted: 2023-12-05
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Duration of ventilation within a predefined range of acceptable respiratory parameters
timeFrame: Every 30 seconds for 240 minutes
Secondary outcomes:
measure: Manual adjustments of ventilator settings
timeFrame: Any time the manual adjustment is performed throughout the 4-hour study period
measure: Physiological data - blood pressure
timeFrame: Mean hourly for 4 hours
measure: Physiological data - respiratory rate
timeFrame: Mean hourly for 4 hours
measure: Physiological data - heart rate
timeFrame: Mean hourly for 4 hours
measure: Biochemical data - pH
timeFrame: Upon intubation, at 1-hour, 2-hour, 3-hour and 4-hour
measure: Biochemical data - CO2 and O2
timeFrame: Upon intubation, at 1-hour, 2-hour, 3-hour and 4-hour
measure: Biochemical data - bicarbonate
timeFrame: Upon intubation, at 1-hour, 2-hour, 3-hour and 4-hour
measure: Patient outcome - mechanical ventilation
timeFrame: Assessed from time of intubation to time of successful extubation or death from any cause, whichever came first, assessed up to 28 days
measure: Patient outcome - LOS ED
timeFrame: Assessed from time of triage to time patient leaves ED or death, whichever comes first, up to 7 days
measure: Patient outcome - LOS ICU
timeFrame: Assessed from time of admission into the ICU to time of transfer to general ward or death, whichever comes first up to 28 days
measure: Patient outcome - LOS hospital
timeFrame: Assessed from time of triage in ED to time of discharge or in-hospital death, whichever comes first up to 28 days
measure: Mortality rate
timeFrame: At 14 and 28 days after recruitment
measure: Number of patients developing ARDS and pneumothorax
timeFrame: At anytime within the 4-hour intervention or upon discharge or diagnosis of complications
measure: Ventilator data - airway pressures
timeFrame: Every 30 seconds for 240 minutes
measure: Ventilator data - FiO2
timeFrame: Every 30 seconds for 240 minutes
Other outcomes:
Locations:
Study officials:
affiliation: University of Malaya
name: Khadijah Poh, MMed
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lellouche F, Bouchard PA, Simard S, L'Her E, Wysocki M. Evaluation of fully automated ventilation: a randomized controlled study in post-cardiac surgery patients. Intensive Care Med. 2013 Mar;39(3):463-71. doi: 10.1007/s00134-012-2799-2. Epub 2013 Jan 22.
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citation: Angotti LB, Richards JB, Fisher DF, Sankoff JD, Seigel TA, Al Ashry HS, Wilcox SR. Duration of Mechanical Ventilation in the Emergency Department. West J Emerg Med. 2017 Aug;18(5):972-979. doi: 10.5811/westjem.2017.5.34099. Epub 2017 Jul 11.
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citation: Clavieras N, Wysocki M, Coisel Y, Galia F, Conseil M, Chanques G, Jung B, Arnal JM, Matecki S, Molinari N, Jaber S. Prospective randomized crossover study of a new closed-loop control system versus pressure support during weaning from mechanical ventilation. Anesthesiology. 2013 Sep;119(3):631-41. doi: 10.1097/ALN.0b013e3182952608.
citation: Chelly J, Mazerand S, Jochmans S, Weyer CM, Pourcine F, Ellrodt O, Thieulot-Rolin N, Serbource-Goguel J, Sy O, Vong LVP, Monchi M. Automated vs. conventional ventilation in the ICU: a randomized controlled crossover trial comparing blood oxygen saturation during daily nursing procedures (I-NURSING). Crit Care. 2020 Jul 22;24(1):453. doi: 10.1186/s13054-020-03155-3.