Does Automated Closed-Loop Ventilation Reduce the DRiving Pressure Levels in Patients With ARDS (AiRDRoP)

March 4, 2019 updated by: Prof. Dr. Marcus J. Schultz, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Does Automated Closed-Loop Ventilation Reduce the DRiving Pressure Levels in Patients With ARDS (AiRDRoP) - a Single-Center Crossover Study and Randomized Controlled Trial

The objective of this crossover study and randomized controlled trial (RCT) is to compare ΔP levels during INTELLiVENT®-ASV with conventional lung protective ventilation in the acute and sub-acute phase of moderate or severe ARDS.

A total of 48 adult patients admitted to intensive care units with moderate or severe ARDS will be included. In the acute phase patients will receive 4 hours of INTELLiVENT-ASV ventilation and 4 hours of conventional lung protective ventilation in random order. After these two blocks the patients are allocated into either the INTELLiVENT-ASV arm or the conventional lung protective ventilation arm.

in the sub-acute phase patients will be assessed every day until day 7 or extubation, whichever comes first.

Primary endpoint is the transpulmonary transpulmonary (ΔP). Secondary endpoints of both studies include other ventilator settings and ventilation parameters, as well as time spent at a ΔP level of 15 cm H2O or higher.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

- Objective:

The objective of this crossover study and randomized controlled trial (RCT) is to compare ΔP levels during INTELLiVENT®- adaptive support ventilation (ASV) with conventional lung protective ventilation in the acute and sub-acute phase of moderate or severe ARDS.

- Study design:

Single center crossover study (in the acute phase) and RCT (in the sub-acute phase).

- Study population:

The study population consists of 48 consecutive intubated and ventilation patients with moderate or severe ARDS according to the Berlin definition with an anticipated duration of mechanical ventilation of > 24 hours.

- Sample size calculation:

The sample size is computed based on the hypothesis that ventilation with INTELLiVENT®-ASV is associated with a reduction in the ΔP level of 5 cm H2O. We based this power calculation on unpublished data from a published cohort of ARDS patients29 and data from an abstract31.

For the RCT, a sample size of 20 patients in each group has 90% statistical power to detect a difference in the ΔP level of 5 cm H2O, with means of 15 and 10 cm H2O, respectively, assuming an effect size (f) of 0.4 using a repeated measures ANOVA with a 0.05 two-sided significance level.

The sample size is increased by 20% to correct for early dropouts (i.e., before day 7) and patients in whom it is impossible to measure the ΔP level, meaning that each group will contain 24 patients. Therefore, the total sample size of this study will be 48 patients.

We expect less variation in the crossover than in the RCT. Next, in this part of the study patients serve as their own control. Therefore, with this sample size we will have sufficient power for the crossover.

- Patient allocation:

Crossover study - Data will be collected during two blocks of four hours; one block of conventional lung protective ventilation, and one block of INTELLiVENT®-ASV. The two blocks will take place in randomized order. Both ventilation strategies are frequently used in our ICU. INTELLiVENT®-ASV is a relatively new ventilatory mode that was successfully implemented in our intensive care unit in 2016, especially in patients with ARDS.

Randomized controlled trial - After the crossover, patients are randomly allocated to conventional lung protective ventilation5, meaning that the ventilator is set to pressure controlled mode, or INTELLiVENT®-ASV.

- Ventilator settings:

Cross-over study

During conventional lung protective ventilation, the attending physician sets the ventilator according to the local ventilation protocol. The fraction of inspired oxygen (FiO2) is adjusted to maintain an oxygen saturation of 92 to 96% and/or a PaO2 of > 8 kPa. The respiratory rate is adjusted to maintain a blood pH of 7.25 to 7.45. The lowest level of positive end-expiratory pressure (PEEP) is 5 cm H2O; allowed PEEP-FiO2 are in concordance with the ARDS network recommendations;5 these combinations are based on two large RCTs in ARDS patients, and is standard practice in our unit.

During INTELLiVENT®-ASV, the attending physician sets the target for et-CO2 to maintain a blood pH of 7.25 to 7.45. The target for oxygen saturation is set at 92- 96%. The lowest level of PEEP is kept at 5 cm H2O.

Of note, INTELLiVENT®-ASV is available on all ventilators used in patients with ARDS. Since both ventilation strategies can be applied with these ventilators, there is no need to disconnect a patient from the ventilator. Also, switching between ventilatory modes is a standard procedure in our ICU. However, for the purpose of this study it is protocolized.

Randomized controlled trial

Settings are similar for the RCT as for the crossover study.

- Statistical analysis:

Primary study parameters

The primary outcome, the (transpulmonary) ΔP level, is analyzed using a repeated measures ANOVA. The effect mediation of ventilator parameters on the (transpulmonary) ΔP is analyzed by mediation analysis. P-values of 0.05 are used for statistical significance. When appropriate, statistical uncertainty will be expressed by the 95% confidence levels. All statistical analysis will be performed with the R language and environment for statistical computing.

Secondary study parameters

Continuous normally distributed variables will be expressed by their mean and standard deviation or when not normally distributed as medians and their interquartile ranges. Categorical variables will be expressed as n (%). To test groups Student's t test will be used, if continuous data is not normally distributed the Mann-Whitney U test will be used. Categorical variables will be compared with the Chi-square test or Fisher's exact tests. Time dependent data will be analyzed using a proportional hazard model adjusted for possible imbalances of patients' baseline characteristics. Analysis will be performed with R statistics version 3.0.2. Patient characteristics will be compared and described by appropriate statistics.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Admission to the ICU of the AMC
  • Intubated and mechanically ventilated
  • Within 24 hours of initial diagnosis of ARDS
  • Moderate or severe ARDS (according to the Berlin definition for ARDS)

Exclusion Criteria:

  • Age < 18 years
  • Patients previously included in this study
  • Patients participating in other interventional trials that could influence ventilator settings and ventilation parameters
  • Patients with suspected or confirmed pregnancy
  • Patients with increased (of > 15 mmHg) or uncontrollable intracranial pressure
  • Patients in whom esophageal pressure measurement is contra-indicated (severe bleeding diathesis, suspicion of or known pharyngeal or esophageal obstruction, esophageal ulcers, varices or strictures)
  • Moribund patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Conventional lung protective ventilation
Use of conventional lung protective ventilation, according to the ARDSnet guidelines
Other: Conventional lung protective ventilation
Lung protective ventilation according to the ARDSnet guidelines
Active Comparator: INTELLiVENT-ASV
Use of INTELLiVENT-ASV
Device: INTELLiVENT-ASV
INTELLiVENT-ASV, with software 2.60
Other Names:
  • automated closed-loop ventilation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Transpulmonary driving pressure level
Time Frame: during the course of mechanical ventilation (max. 7 days)
The driving pressure of the lungs system, difference between end-inspiratory and end-expiratory pressure
during the course of mechanical ventilation (max. 7 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Respiratory system driving pressure level
Time Frame: during the course of mechanical ventilation (max. 7 days)
The driving pressure of the respiratory system, difference between Pplat and PEEP
during the course of mechanical ventilation (max. 7 days)
Tidal volume
Time Frame: during the course of mechanical ventilation (max. 7 days)
Volume of a breath
during the course of mechanical ventilation (max. 7 days)
PEEP level
Time Frame: during the course of mechanical ventilation (max. 7 days)
Positive end-expiratory pressure
during the course of mechanical ventilation (max. 7 days)
Pplat level
Time Frame: during the course of mechanical ventilation (max. 7 days)
Plateau pressure
during the course of mechanical ventilation (max. 7 days)
Ppeak level
Time Frame: during the course of mechanical ventilation (max. 7 days)
Peak pressure
during the course of mechanical ventilation (max. 7 days)
RRset
Time Frame: during the course of mechanical ventilation (max. 7 days)
set respiratory rate
during the course of mechanical ventilation (max. 7 days)
RRmeasured
Time Frame: during the course of mechanical ventilation (max. 7 days)
measured respiratory rate
during the course of mechanical ventilation (max. 7 days)
FiO2
Time Frame: during the course of mechanical ventilation (max. 7 days)
Fraction of inspired oxygen
during the course of mechanical ventilation (max. 7 days)
etCO2
Time Frame: during the course of mechanical ventilation (max. 7 days)
end tidal carbondioxide
during the course of mechanical ventilation (max. 7 days)
spO2
Time Frame: during the course of mechanical ventilation (max. 7 days)
peripheral oxygen saturation
during the course of mechanical ventilation (max. 7 days)
VCO2
Time Frame: during the course of mechanical ventilation (max. 7 days)
volume of expired oxygen
during the course of mechanical ventilation (max. 7 days)
PaCO2
Time Frame: during the course of mechanical ventilation (max. 7 days)
Partial pressure of arterial carbondioxide
during the course of mechanical ventilation (max. 7 days)
PaO2
Time Frame: during the course of mechanical ventilation (max. 7 days)
Partial pressure of arterial oxygen
during the course of mechanical ventilation (max. 7 days)
saO2
Time Frame: during the course of mechanical ventilation (max. 7 days)
arterial oxygen saturation
during the course of mechanical ventilation (max. 7 days)
pH
Time Frame: during the course of mechanical ventilation (max. 7 days)
acidity of the arterial blood
during the course of mechanical ventilation (max. 7 days)
HCO3
Time Frame: during the course of mechanical ventilation (max. 7 days)
Bicarbonate
during the course of mechanical ventilation (max. 7 days)
Time spent at high driving pressure
Time Frame: during the course of mechanical ventilation (max. 7 days)
Time spent at a driving pressure of more than 14 cm H2O
during the course of mechanical ventilation (max. 7 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hamilton Medical AG

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marcus J Schultz, MD, PhD, Department of Intensive Care, Academic Medical Center, University of Amsterdam
  • Study Chair: Ary Serpa Neto, MD, MSc, Department of Intensive Care, Academic Medical Center, University of Amsterdam, The Netherlands
  • Study Director: David MP van Meenen, MD, MSc, Department of Intensive Care, Academic Medical Center, University of Amsterdam
  • Study Chair: Marcello Gama de Abreu, MD, PhD, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Germany
  • Principal Investigator: Paolo Pelosi, MD, PhD, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Italy
  • Principal Investigator: Jitske R Rogmans, Department of Intensive Care, Academic Medical Center, University of Amsterdam
  • Principal Investigator: Lennard HL Pennekamp, Department of Intensive Care, Academic Medical Center, University of Amsterdam
  • Principal Investigator: Frank C Dullemeijer, Department of Intensive Care, Academic Medical Center, University of Amsterdam
  • Principal Investigator: Marco Maggiorini, MD, PhD, Department of Intensive Care, Universitatsspital, Zurich
  • Study Chair: Dominik Novotni, MD, PhD, Hamilton Medical AG
  • Principal Investigator: Alexandra Gerlach, Hamilton Medical AG
  • Study Chair: Job BM van Woensel, MD, PhD, Department of Intensive Care, Academic Medical Center, University of Amsterdam
  • Study Chair: Jean-Michel Arnal, MD, PhD, Department of Intensive Care, Intercommunal hospital, Toulon
  • Principal Investigator: Patricia Rocco, MD, PhD, Laboratory of pulmonary investigation, Federal University, Rio de Janeiro
  • Principal Investigator: Dave A Dongelmans, MD, PhD, Department of Intensive Care, Academic Medical Center, University of Amsterdam

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 3, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 6, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 7, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 5, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 4, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AiRDRoP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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