Low Frequency, Ultra-low Tidal Volume Ventilation in Patients With ARDS and ECMO

Study Overview
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Brief Summary
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The acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure, presented in 10% of all intensive care patients and carrying a high mortality rate. Extracorporeal membrane oxygenation (ECMO) is a rescue treatment for patients with severe ARDS. Mechanical ventilator settings in patients with severe ARDS during ECMO therapy are not clearly defined at the moment.

Detailed Description
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The aim of this study is to assess the effect of a rigorous low breathing frequency and ultra-low tidal volume ventilation strategy on clinical outcome, compared to standard ventilator settings following the recent guidelines in patients with severe ARDS treated with ECMO. The hypothesis is that a low breathing frequency and ultra-low tidal volume ventilation strategy is more protective for the ARDS challenged lung and reduces the duration of mechanical ventilation and so increases the ventilator free days in patients with severe ARDS treated with ECMO.

Official Title
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Low Frequency, Ultra-low Tidal Volume Ventilation in Patients With Severe Acute Respiratory Distress Syndrome and Extracorporeal Membrane Oxygenation: a Prospective, Randomized, Clinical Trial

Conditions
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ARDS, Acute Lung Injury, Extracorporeal Membrane Oxygenation, Respiratory Distress Syndrome, Respiratory Tract Diseases, Lung Diseases, Lung Injury, Acute

Intervention / Treatment
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* Other: Ultra-protective ventilator settings
* Other: Standard ventilator settings


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe ARDS - Partial pressure of oxygen/Fraction of inspired oxygen (PaO2/FiO2) < 200 mmHg ECMO < 24 hours in situ Gender-matched Age-matched Exclusion Criteria: BMI > 40 Expected weaning of ECMO < 3 days (postoperative ECMO) Combustion Restrictive chest wall impairment Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Interventional Model Description: Comparison of 2 groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention group<br>Ultra-protective ventilator settings in patients with ARDS and ECMO. | Other: Ultra-protective ventilator settings<br>* 4-5 Breaths per minute; 14-16 cmH2O Positive endexpiratory pressure (PEEP) (adjust PEEP to 23 < Plateau pressure < 25 cmH2O); 23-25 cmH2O Plateau pressure (adjust to not exceed Tidal volume > 4 mL/kg Predicted body weight (PBW)); < 4mL/kg PBW Tidal volume; 1:5 Inspiration:Expiration (I:E)<br>|
| Active Comparator: Control group<br>Standard ventilator settings in patients with ARDS and ECMO. | Other: Standard ventilator settings<br>* 12-25 Breaths per minute; 8-12 cmH2O PEEP; max. 35 cmH2O Plateau pressure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator free days | Ventilator free days | Immediately after initiation of ECMO up to 28 days | 
| Time from randomization to fulfillment of extubation criteria | Time from randomization (initiation of ECMO) to fulfillment of the extubation criteria: ARDS resolved Temperature ≥ 36°C and ≤ 39°C Low FiO2 (< 0.5) PEEP (< 8 cmH2O) requirement Able to initiate spontaneous breaths Tidalvolume > 5 mL/kg or > 325 mL Minute ventilation 5-6 L/min PaO2/FiO2 > 200 mmHg pH ≥ 7.25 Ability to cough after deflating tube cuff Respiratory rate 8-30/min Hemodynamic stability | Immediately after initiation of ECMO up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total time of mechanical ventilation | Total time of mechanical ventilation | Start of mechanical ventilation up to 28 days | 
| 28 day mortality | Mortality from initiation of ECMO till day 28 after initiation of ECMO | Immediately after initiation of ECMO up to 28 days | 
| One year mortality | Mortality from initiation of ECMO till one year after initiation of ECMO | Immediately after initiation of ECMO up to one year | 
| Incidence of reintubation | Incidence of reintubation | Immediately after initiation of ECMO up to 28 days | 
| Length of ICU stay | Length of ICU stay | Immediately after initiation of ECMO | 
| Evaluation of RAS, ACE, ACE2. | Analyses of leftover blood. Renin angiotensin system (RAS) and Angiotensin converting enzyme (ACE) evaluation. | 2 months | 
| Evaluation of Cytokines in pg/ml | IL-6, IL-8, TNFR1, RAGE, Protein C | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, ECMO, Ventilation