Effect of Automated Closed-Loop Ventilation Versus Conventional Ventilation on Duration and Quality of Ventilation

Not Applicable

Recruiting

• Conditions: Quality of Breathing; Ventilator-free Days
• Interventions: Procedure: CONVENTIONAL VENTILATION; Procedure: INTELLiVENT-ASV

• Registration Number: NCT04593810
• Lead Sponsor: Prof. Dr. Marcus J. Schultz

Brief Summary

INTELLiVENT-Adaptive Support Ventilation (ASV) is a fully automated closed-loop mode of mechanical ventilation available on commercial ventilators. Evidence for clinical benefit of INTELLiVENT-ASV in comparison to non-automated ventilation is lacking.

The ACTiVE study is an international, multicenter, randomized controlled trial in invasively ventilated ICU patients with the objective to compare INTELLiVENT-ASV to conventional ventilation. We hypothesise that INTELLiVENT-ASV shortens the duration of ventilation. The secondary hypothesis is that INTELLiVENT-ASV improves the quality of breathing.

Detailed Description

Objective

The primary objective of this trial is to compare INTELLiVENT-ASV with non-automated ventilation in critically ill intensive care unit (ICU) patients with respect to ventilation duration. One secondary aim is to test whether INTELLiVENT-ASV improves quality of breathing, expressed as the proportion of breath within lung-protective margins, in a time frame of 24 hours early after start of invasive ventilation.

Study design

International, multicenter, superiority randomized clinical trial in critically ill, intubated and ventilated adult ICU patients with an anticipated duration of ventilation of at least 24 hours.

Study population

Adult patients admitted to ICUs in the Netherlands and Italy.

Sample size calculation

The sample size is based on the hypothesis that INTELLiVENT-ASV will shorten ventilation duration by 1.5 days with no changes in mortality rate. Based on previously performed studies a sample of 1,200 patients (600 in each treatment group) is needed to have beta of 80% power and a two-tailed alpha of 0.05, to detect a mean between-group difference of 1.5 VFD-28, allowing a dropout rate of 5%. By including 1,200 patients, this study will be sufficiently powered to detect differences in the secondary endpoint, which is quality of breathing.

Methods:

Within one hour of start of ventilation in the ICU, patients are randomly assigned in a 1:1 ratio to INTELLiVENT-ASV or non-automated ventilation. Randomization will be stratified by center. As soon as possible after randomization, but within a maximum of 72 hours, deferred consent is obtained from the legal representative of the patient.

INTELLiVENT-ASV In patients who are randomized to INTELLiVENT-ASV, the ventilator is switched to this fully automated mode as soon possible. The sensors for end-tidal carbon dioxide (ETCO2) and pulse oximetry (SpO2) are connected and activated in the ventilator. Patient's gender and height are set on the ventilator and patient condition is chosen if applicable. If needed, the targets zones for ETCO2 and SpO2 are adjusted. The default alarm limits are accepted.

It is advised to enable QuickWean in all patients. The use of the automated Spontaneous Breathing Trial (SBT) function is left to the discretion of the clinician.

CONVENTIONAL VENTILATION Patients who are randomized to conventional ventilation will be ventilated with a mode that is not fully automated, thus standard volume controlled (VCV) or pressure controlled ventilation (PCV), and pressure support ventilation (PSV), depending on patient's activity. None of the following semi or fully automated modes of ventilation is allowed at any time: Neurally Adjusted Ventilatory Assist (NAVA), SmartCare/PS, Proportional Assist Ventilation (PAV), or the predecessor of INTELLiVENT-ASV named ASV.

In all patients who receive assist ventilation (i.e., VCV or PCV), three times a day it should be checked whether the patient can accept supported ventilation (i.e., PSV); this should also be tried when the patient shows respiratory muscle activity during assist ventilation, or in case of patient-ventilator asynchrony.

Patients can be subjected to SBTs using either a T-piece or ventilation with minimal support (pressure support level \< 10 cm H2O). An SBT is deemed successful when the following criteria are met for at least 30 minutes, i.e., respiratory rate \< 35/min, peripheral oxygen saturation \> 90%, increase \< 20% of heart rate and blood pressure, and no signs of anxiety and diaphoresis.

In both groups patients are extubated if standard extubation criteria are fulfilled, i.e., normal body temperature, patient awake and responsive/cooperative, adequate cough reflex, adequate oxygenation, hemodynamically stable, and adequate lung function.

Study Timeline

• Study First Submitted: 2020-10-11
• Study Start: 2020-10-19
• Study First Submitted QC: 2020-10-19
• Study First Posted: 2020-10-20
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-14
• Last Update Posted: 2025-01-15
• Primary Completion: 2025-03-01
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

• admission to one of the participating ICUs
• intubated and receiving invasive ventilation
• anticipated duration of ventilation of at least 24 hours

Exclusion Criteria

• age below 18 years
• patients with suspected or confirmed pregnancy
• invasive ventilation > 1 hour in the ICU
• invasive ventilation > 6 hours directly preceding the current ICU admission
• participation in another interventional trial using similar endpoints
• after recent pneumectomy or lobectomy
• morbid obesity (body mass index > 40 kg/m2)
• premorbid restrictive pulmonary disease
• unreliable pulse oximetry (secondary to carbon monoxide poisoning or sickle cell disease)
• any neurologic diagnosis that can prolong duration of mechanical ventilation, e.g., Guillain-Barré syndrome, high spinal cord lesion or amyotrophic lateral sclerosis, multiple sclerosis, or myasthenia gravis
• patients receiving or planned to receive veno-venous, veno-arterial or arterio-venous extracorporeal membrane oxygenation (ECMO)
• unavailability of INTELLiVENT-ASV (no ventilator available with this ventilation mode)
• previously randomized in this study
• no informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional ventilation	CONVENTIONAL VENTILATION	Use of conventional ventilation after intubation and during all mechanical ventilation in the ICU.
INTELLiVENT-ASV	INTELLiVENT-ASV	Use of INTELLIVENT-ASV after intubation and during all mechanical ventilation in the ICU.

Primary Outcome Measures

Name	Time	Method
Ventilator-free days and alive at day 28	first 28 days after start of ventilation	The number of days from day 1 to day 28 the patient is alive and breathes without assistance of the mechanical ventilator, if the period of unassisted breathing lasted at least 24 consecutive hours

Secondary Outcome Measures

Name	Time	Method
Mortality	first 90 days after start of ventilation	Any death during ICU- or hospital-stay, at day 28 and day 90
Quality of Life questionnaire	day 28 after start of ventilation	The European Quality of life 5 Dimensions 5 Levels questionnaire (EQ-5D-5L) is used to assess health-related quality of life status in adults. It consists of five dimensions (Mobility, Self-care, Usual activities, Pain \& discomfort, Anxiety \& depression), each of which has five severity levels (from 1 to 5) that are described by statements appropriate to that dimension. Higher values mean worse quality of life. The evaluation includes a visual analogue scale to quantitative measure the overall health status. This scale has a range from 0 to 100.
Quality of breathing	24 hours early after start of invasive ventilation.	Proportion of breaths within lung-protective margins
Duration of ventilation	first 28 days after start of ventilation	Duration of ventilation in survivors
Length of stay	first 90 days after start of ventilation	Length of stay in the intensive care unit and in the hospital
Pulmonary complications	daily until ICU discharge or day 28	Development of ARDS, severe hypoxemia, severe hypercapnia, severe atelectasis, pneumothorax and ventilator-associated pneumonia
Rescue therapies for severe hypoxemia or severe atelectasis	daily until ICU discharge or day 28	Incidence of use of rescue therapies for severe hypoxemia or severe atelectasis: recruitment maneuver, prone positioning, bronchoscopy for opening atelectasis
Extubation failure	daily until ICU discharge or day 28	Extubation with need for reintubation within 24 hours
Maximal inspiratory pressure (MIP)	within 24 hours after extubation	Maximal inspiratory pressure measured after extubation at centers that can collect this data

Trial Locations

Locations (10)

Ospedale Policlinico San Martino; 🇮🇹 Genua, Italy

Policlinico San Matteo Fondazione IRCCS; 🇮🇹 Pavia, Italy

Academic Medical Center, Intensive Care; 🇳🇱 Amsterdam, Netherlands

Flevoziekenhuis; 🇳🇱 Almere, Netherlands

Reinier de Graaf Gasthuis; 🇳🇱 Delft, Netherlands

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

Canisius-Wilhelmina Hospital; 🇳🇱 Nijmegen, Netherlands

Leiden UMC; 🇳🇱 Leiden, Netherlands

Elisabeth-TweeSteden Ziekenhuis; 🇳🇱 Tilburg, Netherlands

Diakonessenhuis, Utrecht; 🇳🇱 Utrecht, Netherlands