ART-2 Pilot - Driving Pressure Limited Ventilation for Patients With ARDS

Study Overview
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Brief Summary
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This is a multicenter randomized controlled pilot trial to investigate the feasibility of a driving pressure limited mechanical ventilation strategy compared to the ARDS Clinical Network strategy (conventional strategy) in patients with acute respiratory distress syndrome (ARDS).

Detailed Description
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Mechanical ventilation has the potential to produce or worsen alveolar injury. Driving pressure is the difference between plateau pressure and PEEP. Evidence from observational studies suggests that elevated driving pressure is the main independent determinant of ventilator-induced lung injury, however clinical trials are needed to establish whether targeting low driving pressures can improve clinical outcomes in patients with acute respiratory distress syndrome (ARDS). Thus, ART2pilot is a multicenter randomized controlled trial to assess the feasibility of a driving pressure limited mechanical ventilation strategy compared to the ARDS Clinical Network strategy (conventional strategy) in patients with ARDS. Patients considered to this trial are those in mechanical ventilation with diagnosis of ARDS of less than 72 hours duration. We will exclude patients with less than 18 years old; contraindication to hypercapnia such as intracranial hypertension or recent acute coronary syndrome; patients in which a high probability of death within 24 hours is anticipated and patients under exclusive palliative care. Eligible patients will be randomized to the driving pressure limited ventilation strategy or ARDSNet strategy. The primary outcome is driving pressure between days 1 and 3.

Official Title
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ART-2 Pilot: A Controlled, Randomized Trial to Assess the Feasiblity of a Driving Pressure Limited Ventilation vs. Standard Strategy (ARDSNet) in Patients With ARDS

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Other: Driving pressure limited ventilation
* Other: Conventional ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients on invasive mechanical ventilation with diagnosis of ARDS of less than 72 hours duration. Exclusion criteria: Less than 18 years old. Presence of any contraindication to hypercapnia as suspected or confirmed intracranial hypertension or recent (<7 days) acute coronary syndrome. Patients in which a high probability of death within 24 hours is anticipated. Patients under exclusive palliative care.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Driving pressure limited ventilation<br>Driving pressure limited ventilation | Other: Driving pressure limited ventilation<br>* We will use volume controlled ventilation or pressure support in the weaning phase. We will adjust tidal volume between 3 and 8 mL/Kg of predicted body weight in order to achieve a driving pressure of 13 cmH2O. The respiratory rate will be titrated to achieve a pH between 7.30 and 7.45 (maximum respiratory rate is 50 breathings per minute). We will not limit plateau pressure in this arm.<br>|
| Active Comparator: Conventional ventilation<br>Mechanical ventilation as proposed in the ARDSNet protocol. | Other: Conventional ventilation<br>* ARDSNet Strategy: conventional mechanical ventilation strategy with tidal volume between 4 and 6 mL/kg of predicted body weight and plateau pressure limited to 30 cmH2O.<br>* Other names: ARDSNet strategy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean driving pressure between day 1 and day 3 | Driving pressure is the difference between plateau pressure and PEEP. It will be measured every morning in patients without spontaneous efforts. As every patients will have up to three measurements, we will consider the mean driving pressure for each patient. | Day 1 to Day 3 after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to study procedures: daily adjustement of driving pressure in experimental group and tidal volume in the control group |  | Days 1 to 7 | 
| Rate of driving pressure equal or lower than 13cmH2O |  | Days 1 to 3 after randomization | 
| Mean PEEP from day 1 to 7 |  | Days 1 to 7 | 
| Mean tidal volume from day 1 to day 7 |  | Days 1 to 7 | 
| Mean static compliance of the respiratory system from day 1 to day 7 |  | Days 1 to 7 | 
| Mean plateau pressure from day 1 to day 7 |  | Days 1 to 7 | 
| Mean driving pressure from day 1 to day 7 |  | Days 1 to 7 | 
| Mean respiratory rate from day 1 to day 7 |  | Days 1 to 7 | 
| Barotrauma |  | Days 1 to 7 | 
| Severe acidosis (pH <7.1) |  | Days 1 to 7 | 
| Other adverse events |  | Days 1 to 7 | 
| Length of stay in intensive care unit |  | ICU stay | 
| Length of stay in hospital |  | In-hospital stay | 
| Mechanical ventilation free days from day 0 to day 28 |  | From day 0 to day 28 | 
| ICU mortality |  | ICU stay | 
| In-hospital mortality |  | Hospital stay | 
| 28-day survival |  | From day 0 to day 28 |