Inflammation During ECMO Therapy and ECMO Weaning

Study Overview
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Brief Summary
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The goal of this interventional clinical trial is to compare patients who undergo ECMO therapy for treatment of acute respiratory distress syndrome (ARDS) and a randomized into one of two possible weaning strategy groups. Group 1: Weaning from ventilator occurs before ECMO weaning. Group 2: Weaning from ECMO occurs before weaning from ventilator. This study investigates which one of these strategies is more indulgent for the lung, and leads to less inflammation and therefore less potential side effects and an overall more favourable clinical course. As a primary criterion, measure of IL-6 in blood samples will beused. As secondary criterions, SOFA score at various time points, ventilation pressures, lung injury score (LIS), length of stay in the intensive care unit, and ventilator-associated pneumonia as well as levels of inflammatory cells and cytokines in both blood samples and bronchoalveolar lavage at different time points will be determined.

Official Title
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Inflammation During ECMO Therapy and ECMO Weaning

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Procedure: Ventilator weaning first
* Procedure: ECMO weaning first


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute respiratory distress syndrome (ARDS) according to the Berlin Definition (PaO2/FiO2 < 100) and treatment with veno-venous ECMO (vvECMO) Hemodynamic stability Lung compliance did not change/improved during the last 24 hours Tidal volume did not change/improved during the last 24 hours with a PEEP of 10 cmH20 or above Consent of the patient or their legal representative Exclusion Criteria: Age < 18 years Artificial ventilation for more than 7 days prior Patient, legal representative or doctors decided against an unrestricted intensive care treatment Positive pregnancy test at time of screening Cardiac failure requiring veno-arterial ECMO therapy Chronic respiratory insufficiency requiring long-term oxygen treatment

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 |
| --- | --- |
| Active Comparator: Ventilator weaning first<br> | Procedure: Ventilator weaning first<br>* Ventilator weaning initiated and completed before start of ECMO weaning.<br>|
| Active Comparator: ECMO weaning first<br> | Procedure: ECMO weaning first<br>* ECMO weaning initiated and completed before start of ventilator weaning.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IL-6 concentration (blood samples) | Daily control of above mentioned parameter. | For the duration of the ICU stay, or a maximum of 60 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SOFA-Score | Sequential organ failure assessement score evaluated at days 1-14, 28, and 60. | For the duration of the ICU stay, or a maximum of 60 days at indicated time points as described above.. | 
| Ventilation pressures | Pressures applied to the lung during artificial ventilation | For the duration of the artificial ventilation, or a maximum of 60 days. | 
| Murray Lung Injury Score (LIS) | Assessement of severity of lung damage by the established Lung Injury Score by Murray (Min Value is 0, healthy and Max Value is 20, severly diseased) | For the duration of the ICU stay, or a maximum of 60 days. | 
| Length of stay in the intensive care unit | Length of stay in the intensive care unit. | For the duration of the ICU stay, or a maximum of 60 days. | 
| Ventilator-associated pneumonia | Occurence/incidence of ventilator-associated pneumonia. | For the duration of the ICU stay, or a maximum of 60 days. | 
| Cytokines and inflammatory cells in blood samples (IL-1beta, Il-10 and TNF-alpha) | Collection of blood samples at various times points for further analysis. | For the duration of the ICU stay, or a maximum of 60 days. | 
| Cytokines and inflammatory cells in bronchoalveolar lavage (IL-1beta, Il-10 and TNF-alpha) | Collection of bronchoalveolar lavage samples at various times points for further analysis. | For the duration of the ICU stay, or a maximum of 60 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, Extracorporal membrane oxygenation, Extracorporal membrane oxygenation weaning, Ventilation therapy