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

NCT ID: NCT04593810

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-19
• Study Completion Date: 2025-09-16

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.

Conditions

Ventilator-free Days; Quality of Breathing

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

INTELLiVENT-ASV

Use of INTELLIVENT-ASV after intubation and during all mechanical ventilation in the ICU.

Group Type: EXPERIMENTAL

INTELLiVENT-ASV

Intervention Type: PROCEDURE

INTELLiVENT-ASV is activated as soon possible. The sensors for ETCO2 and SpO2 are connected and activated. Patient's gender and height are set on the ventilator and patient condition is chosen if applicable.

Conventional ventilation

Use of conventional ventilation after intubation and during all mechanical ventilation in the ICU.

Group Type: ACTIVE_COMPARATOR

CONVENTIONAL VENTILATION

Intervention Type: PROCEDURE

Conventional ventilation consists of VCV or PCV and PSV, depending on patient's activity. None of the semi or fully automated modes of ventilation is allowed at any time.

Interventions

INTELLiVENT-ASV

INTELLiVENT-ASV is activated as soon possible. The sensors for ETCO2 and SpO2 are connected and activated. Patient's gender and height are set on the ventilator and patient condition is chosen if applicable.

Intervention Type: PROCEDURE

CONVENTIONAL VENTILATION

Conventional ventilation consists of VCV or PCV and PSV, depending on patient's activity. None of the semi or fully automated modes of ventilation is allowed at any time.

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Catharina Ziekenhuis Eindhoven

OTHER

Sponsor Role: collaborator

Reinier de Graaf Groep

OTHER

Sponsor Role: collaborator

Flevoziekenhuis

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Canisius-Wilhelmina Hospital

OTHER

Sponsor Role: collaborator

Elisabeth-TweeSteden Ziekenhuis

OTHER

Sponsor Role: collaborator

Diakonessenhuis, Utrecht

OTHER

Sponsor Role: collaborator

Ospedale Policlinico San Martino

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: collaborator

Prof. Dr. Marcus J. Schultz

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Marcus J. Schultz

Prof. Dr. Marcus J. Schultz

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Janneke Horn, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Intensive Care, Academic Medical Center

Frederique Paulus, PhD

Role: STUDY_DIRECTOR

Department of Intensive Care, Academic Medical Center

Marcus J Schultz, MD,PhD

Role: STUDY_DIRECTOR

Department of Intensive Care, Academic Medical Center

Locations

Ospedale Policlinico San Martino

Genoa, , Italy

Policlinico San Matteo Fondazione IRCCS

Pavia, , Italy

Flevoziekenhuis

Almere Stad, , Netherlands

Academic Medical Center, Intensive Care

Amsterdam, , Netherlands

Reinier de Graaf Gasthuis

Delft, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

Leiden UMC

Leiden, , Netherlands

Canisius-Wilhelmina Hospital

Nijmegen, , Netherlands

Elisabeth-TweeSteden Ziekenhuis

Tilburg, , Netherlands

Diakonessenhuis, Utrecht

Utrecht, , Netherlands

Countries

Italy; Netherlands

References

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.

Reference Type: DERIVED

PMID: 35461264 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ACTiVE

Identifier Type: -

Identifier Source: org_study_id