ART-3 Pilot - Driving Pressure Limited Ventilation for Patients Without ARDS (ART3pilot)

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 a conventional strategy in patients without 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 without acute respiratory distress syndrome (ARDS). Thus, ART-3 pilot is a multicenter randomized controlled trial to assess the feasibility of a driving pressure limited mechanical ventilation strategy compared to a conventional strategy in patients without ARDS. Patients considered to this trial are those in mechanical ventilation for less than 72 hours without diagnosis of ARDS. 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 conventional strategy (tidal volume of 8 mL/kg of predicted body weight). The primary outcome is driving pressure between days 1 and 3.

Official Title
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ART-3 Pilot: A Randomized Controlled Trial to Assess the Feasiblity of a Driving Pressure Limited Ventilation vs.Standard Strategy in Patients Without ARDS

Conditions
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Mechanical Ventilation, 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 for less than 72 hours and without diagnosis of ARDS, and no perspective of extubation in 24 hours. 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 (≤13cmH2O) | Other: Driving pressure limited ventilation<br>* Investigators will use volume controlled (or pressure support ventilation) and 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). Investigators will not limit plateau pressure in this arm. Once a daily the investigators will assess the target tidal volume that generates a driving pressure of 13cmH2O. The patient should be sedated and without spontaneous efforts during this assessment.<br>|
| Active Comparator: Conventional ventilation<br>Mechanical ventilation with limited tidal volume (8mL/kg of predicted body weight) and plateau pressure (≤30cmH2O) | Other: Conventional ventilation<br>* Investigators will use volume controlled or pressure support ventilation, tidal volume ≤8 mL/kg of predicted body weight and plateau pressure limited to 30 cmH2O.The respiratory rate will be titrated to achieve a pH between 7.30 and 7.45 (maximum respiratory rate is 35 breathings per minute).<br>|

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 |  | From Day 1 to Day 3 after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of investigators adering to study procedures |  | Days 1 to 7 | 
| Rate of driving pressure equal or lower than 13 cmH2O |  | Days 1 to 3 after randomization | 
| Mean of positive end expiratory pressure (PEEP) from day 1 to 7 |  | Days 1 to 7 | 
| Mean tidal volume from day 1 to 7 |  | Days 1 to 7 | 
| Mean static compliance of the respiratory system from day 1 to 7 |  | Days 1 to 7 | 
| Mean plateau pressure from day 1 to 7 |  | Days 1 to 7 | 
| Mean driving pressure from day 1 to 7 |  | Days 1 to 7 | 
| Mean respiratory rate from day 1 to 7 |  | Days 1 to 7 | 
| Number of patients with barotrauma |  | Days 1 to 7 | 
| Mean of severe acidosis (pH <7.1) |  | Days 1 to 7 | 
| Number of patients with other adverse events |  | Days 1 to 7 | 
| Lenght of stay in intensive care unit |  | Patients will be followed during the period of ICU stay, an expected average of 28 days | 
| Lenght of stay in hospital |  | Patients will be followed during the period of hospital stay, an expected average of 28 days | 
| Number of mechanical ventilation free days from day 0 to day 28 |  | From day 0 to day 28 | 
| ICU mortality |  | Patients will be followed during the period of hospital stay, an expected average of 28 days | 
| In-hospital mortality |  | Patients will be followed during the period of hospital stay, an expected average of 28 days | 
| 28-day survival |  | From day 0 to day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patients, ARDS diagnosis