Clinical trial NCT04593810: Effect of Automated Closed-Loop Ventilation Versus Conventional Ventilation on Duration and Quality of Ventilation
Official title: Effect of Automated Closed-Loop Ventilation Versus Conventional Ventilation on Duration and Quality of Ventilation ('ACTiVE') - a Randomized Clinical Trial in Intensive Care Unit Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ventilator-free Days
Quality of Breathing
Keywords: Automated invasive ventilation
Closed-loop invasive ventilation
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Catharina Ziekenhuis Eindhoven
name: Reinier de Graaf Groep
name: Flevoziekenhuis
name: Leiden University Medical Center
name: Canisius-Wilhelmina Hospital
name: Elisabeth-TweeSteden Ziekenhuis
name: Diakonessenhuis, Utrecht
name: Ospedale Policlinico San Martino
name: Fondazione IRCCS Policlinico San Matteo di Pavia
First posted: 2020-10-20
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Ventilator-free days and alive at day 28
timeFrame: first 28 days after start of ventilation
Secondary outcomes:
measure: Quality of breathing
timeFrame: 24 hours early after start of invasive ventilation.
measure: Duration of ventilation
timeFrame: first 28 days after start of ventilation
measure: Length of stay
timeFrame: first 90 days after start of ventilation
measure: Mortality
timeFrame: first 90 days after start of ventilation
measure: Pulmonary complications
timeFrame: daily until ICU discharge or day 28
measure: Rescue therapies for severe hypoxemia or severe atelectasis
timeFrame: daily until ICU discharge or day 28
measure: Extubation failure
timeFrame: daily until ICU discharge or day 28
measure: Maximal inspiratory pressure (MIP)
timeFrame: within 24 hours after extubation
measure: Quality of Life questionnaire
timeFrame: day 28 after start of ventilation
Other outcomes:
Locations:
city: Genua
country: Italy
facility: Ospedale Policlinico San Martino
city: Pavia
country: Italy
facility: Policlinico San Matteo Fondazione IRCCS
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amsterdam
country: Netherlands
facility: Academic Medical Center, Intensive Care
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Leiden
country: Netherlands
facility: Leiden UMC
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Hospital
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden Ziekenhuis
city: Utrecht
country: Netherlands
facility: Diakonessenhuis, Utrecht
Study officials:
affiliation: Department of Intensive Care, Academic Medical Center
name: Janneke Horn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Intensive Care, Academic Medical Center
name: Frederique Paulus, PhD
role: STUDY_DIRECTOR
affiliation: Department of Intensive Care, Academic Medical Center
name: Marcus J Schultz, MD,PhD
role: STUDY_DIRECTOR
References:
citation: Botta M, Tsonas AM, Sinnige JS, De Bie AJR, Bindels AJGH, Ball L, Battaglini D, Brunetti I, Buiteman-Kruizinga LA, van der Heiden PLJ, de Jonge E, Mojoli F, Robba C, Schoe A, Paulus F, Pelosi P, Neto AS, Horn J, Schultz MJ; ACTiVE collaborative group. Effect of Automated Closed-loop ventilation versus convenTional VEntilation on duration and quality of ventilation in critically ill patients (ACTiVE) - study protocol of a randomized clinical trial. Trials. 2022 Apr 23;23(1):348. doi: 10.1186/s13063-022-06286-w.