Airway Pressure Release Ventilation for Moderate-to-severe Acute Respiratory Distress Syndrome (EARL)

January 27, 2022 updated by: Eric Sy, Saskatchewan Health Authority - Regina Area

Early Use of Airway Pressure ReLease Ventilation in Critically Ill Adults With Moderate-to-severe Acute Respiratory Distress Syndrome

This study will examine the feasibility of a large clinical trial investigating the effectiveness of airway pressure release ventilation and low tidal volume ventilation for patients with moderate-to-severe acute respiratory distress syndrome.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acute respiratory distress syndrome (ARDS) is a disease that has an incidence of 5% of hospitalized mechanically ventilated patients. ARDS is associated with high morbidity and mortality in critically ill patients, with mortality reported as high as 45% in severe ARDS. Patients who develop ARDS will require mechanical ventilation. Patients with ARDS are graded by the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) into three categories of severity: mild (PaO2/FiO2 201-300 mm Hg), moderate (PaO2/FiO2 101-200 mmHg), and severe (PaO2/FiO2 ≤ 100).

Volutrauma and barotrauma are thought to contribute to the development of ARDS and alter mortality. The damage that occurs to the lungs manifests itself as inflammation, which leads to poor gas exchange of oxygen and carbon dioxide. Several strategies of lung-protective mechanical ventilation have been investigated in ARDS, including the use of low tidal volume ventilation (LTVV) or ARDSNet strategy, high frequency oscillation ventilation (HFOV), and airway pressure release ventilation (APRV). Lung protective strategies may be best beneficial prior to the onset of the development of ARDS or early in the course of the disease. As a result of the ARDSNet trial, LTVV has been adopted as the usual standard of care of ventilation and safest mode of ventilation for patients with ARDS.

Recently, APRV has been proposed as a potential alternative to LTVV. APRV is a form of ventilation that keeps the lungs inflated through the majority of the breath cycle and allows patients to breathe spontaneously above this level of inflation. APRV allows for spontaneous respiration with increased airway pressure, potentially allowing for decreased sedation, shorter duration of mechanical ventilation, and decreased need for vasopressors. APRV has been associated with possible reduction in incidence of ARDS and in-hospital mortality in non-randomized observational studies. In patients with established ARDS, the use of APRV has also not been well studied, with most studies limited to small observational studies often with no comparison group. One randomized trial using APRV alone had less than 30% of patients having a diagnosis of ARDS and did not show any difference in any outcomes. Recently, Zhou and colleagues conducted a randomized trial comparing APRV to conventional ventilation in 138 mechanically ventilated patients with mild to severe ARDS and found that APRV may shorten the duration of mechanical ventilation and reduce intensive care unit (ICU) length of stay.

While some of these studies had shown promise of APRV compared to LTVV, there has not been acceptance of APRV into guidelines as first line ventilation, and recommendations of institutions such as the Canadian Agency for Drugs and Technology in Health (CADTH) recommends interpreting these results with caution. Consequently, there remains clinical equipoise on this issue. Some ICU clinicians will currently use APRV as a rescue mode of ventilation in ARDS in their clinical practice while others will continue with the use of LTVV. We would like to randomize patients to LTVV or APRV and examine the feasibility of conducting a large multicentre randomized controlled trial in Canada.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • 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

  • Canada
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4P 0W5
        • Regina General Hospital

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Fulfilling the diagnostic criteria of ARDS, according to the Berlin definition
  • Moderate to severe ARDS as defined as a PaO2: FiO2 ratio of ≤150 during invasive mechanical ventilation
  • Endotracheal intubation and mechanical ventilation for ARDS less than 48 hours

Exclusion Criteria:

  • Age less than 18 years
  • Pregnancy
  • Intracranial hypertension (suspected or confirmed)

  • Severe chronic obstructive pulmonary disease as defined by either:

    1. FEV1/FVC less than 50% predicted, or
    2. Chronic hypercarbia (PaCO2>45 mmHg), chronic hypoxemia (PaO2 < 55 mmHg) on room air, and/or elevated admission serum HCO3 >30 mmol/L
  • Presence of documented barotrauma, i.e. pneumothorax
  • Treatment with extracorporeal support (ECMO) at enrollment
  • Refractory shock
  • Advanced directives indicating preferences to not have advanced life support
  • Moribund patient, i.e. not expected to survive longer than 24 hours

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Low tidal volume ventilation
Conventional low tidal volume ventilation
Device: Low tidal volume ventilation
Conventional ventilation strategy for patient with ARDS
Experimental: Airway pressure release ventilation
Early use of airway pressure release ventilation
Device: Airway pressure release ventilation
Experimental ventilation protocol for patients with ARDS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Informed consent rate
Time Frame: Informed consent rate will be measured over a 1 year period of the pilot study
A successful informed consent rate will be defined as ≥70% of substitute decision makers or patients approached choosing to participate in this trial
Informed consent rate will be measured over a 1 year period of the pilot study
Recruitment rate
Time Frame: Recruitment rate will be measured over the one year of the pilot study.
A successful recruitment rate will be achieving at least 15 patients over the 1 year period.
Recruitment rate will be measured over the one year of the pilot study.
Protocol adherence rate
Time Frame: Protocol adherence will be measured for each study patient, and compiled over the duration of the pilot study (i.e. 1 year).
An adherence rate of at least 80% will be considered successful.
Protocol adherence will be measured for each study patient, and compiled over the duration of the pilot study (i.e. 1 year).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
28-day mortality
Time Frame: Up to Day 28
Death, measured from time of enrollment until 28 days.
Up to Day 28
In-hospital mortality
Time Frame: Up to 365 days
Death, at hospital discharge
Up to 365 days
ICU length of stay
Time Frame: Up to 365 days
Length of stay in the intensive care unit
Up to 365 days
Hospital length of stay
Time Frame: Up to 365 days
Length of stay in the hospital in days
Up to 365 days
Length/duration of mechanical ventilation
Time Frame: Up to 365 days
Length of time patient was on mechanical ventilation
Up to 365 days
Incidence of tracheostomy
Time Frame: Up to 365 days
Incidence of tracheostomy during their ICU stay
Up to 365 days

Collaborators and Investigators

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

Sponsor

Saskatchewan Health Authority - Regina Area

Investigators

  • Principal Investigator: Eric J Sy, MD MPH FRCPC, Saskatchewan Health Authority - Regina Area

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

June 29, 2020

Primary Completion (Actual)

December 31, 2021

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

October 26, 2019

First Submitted That Met QC Criteria

November 5, 2019

First Posted (Actual)

November 7, 2019

Study Record Updates

Last Update Posted (Actual)

January 28, 2022

Last Update Submitted That Met QC Criteria

January 27, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REB-19-51

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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