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

Sponsor

Saskatchewan Health Authority - Regina Area (Other)

Overall Status

Completed

CT.gov ID

NCT04156438

Collaborator

(none)

Enrollment

Location

Arms

18.1

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome	Device: Low tidal volume ventilation Device: Airway pressure release ventilation	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 29, 2020

Actual Primary Completion Date :

Dec 31, 2021

Actual Study Completion Date :

Dec 31, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Informed consent rate [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
Recruitment rate [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.
Protocol adherence rate [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

FEV1/FVC less than 50% predicted, or
Chronic hypercarbia (PaCO2>45 mmHg), chronic hypoxemia (PaO2 < 55 mmHg) on room air, and/or elevated admission serum HCO3 >30 mmol/L