Trial of ECMO to De-Sedate, Extubate Early and Mobilise in Hypoxic Respiratory Failure

Study Overview
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Brief Summary
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To determine whether a strategy of adding venovenous ECMO to mechanical ventilation, as compared to mechanical ventilation alone, increases the number of intensive care free days at day 60, in patients with moderate to severe acute hypoxic respiratory failure.

Detailed Description
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Mechanically ventilated patients with moderate to severe acute hypoxic respiratory failure are at increased risk of dying, short and long-term health problems and are often very costly to treat. The mechanical ventilator, whilst often lifesaving, may harm patients in two ways i) directly via damage to the lungs (termed ventilator induced lung injury), and ii) indirectly via paralysis and sedation that patients require to tolerate mechanical ventilation. Paralysis and sedation can increase the risk of secondary infections, weakness, prolonged duration of intensive care, as well as long-term physical disability. There is a need to develop new treatments that support patients and at the same time reduce these complications. Extracorporeal membrane oxygenation (ECMO) is a device that supports the lungs by adding oxygen and removing carbon dioxide from the blood. By providing non pulmonary gas exchange, veno-venous (VV) ECMO can reduce the need for the mechanical ventilator. This in turn can reduce the risk of lung damage, and also removes the need for sedating medications so that activities like physiotherapy can begin earlier. The REDEEM trial is a phase 2, investigator initiated, multicentre randomised controlled trial that will recruit 140 patients with moderate to severe acute hypoxic respiratory failure. It is designed to test whether adding ECMO to the mechanical ventilator, as compared to using the mechanical ventilator on its own, leads to an increase in the number of patients who survive and are discharged earlier from the intensive care unit. If the REDEEM trial confirms adding ECMO is more effective than mechanical ventilation alone, it has the potential to change the current paradigm of intensive care treatment of hypoxic respiratory failure, and could lead to changes in practice globally.

Official Title
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A Randomised Controlled Trial of ECMO to De-Sedate, Extubate Early and Mobilise in Hypoxic Respiratory Failure

Conditions
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Mechanical Ventilation Complication, Hypoxemia, Acute Respiratory Distress Syndrome Due to COVID-19, COVID-19 Respiratory Infection, Pneumonia, Extracorporeal Membrane Oxygenation

Intervention / Treatment
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* Other: Venovenous ECMO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mechanically ventilated for hypoxic respiratory failure Mechanical ventilation for ≥3days Moderate to severe respiratory failure on the day of inclusion, as demonstrated by: PaO2:FiO2 Ratio <150 for >6 hours despite protective lung ventilation (including tidal volume <6mls/kg predicted body weight), Trial of proning according to local protocol. Exclusion Criteria: Mechanical ventilation duration >7days Need for immediate VV ECMO Clinical Frailty Score of >4 Patient being actively weaned from mechanical ventilation Requirement for veno-arterial (VA) ECMO Severe coagulopathy (INR≥2.0, platelets < 100 or activated partial thromboplastin time (APTT) >50 seconds) Vascular access not suitable for ECMO (includes inferior vena cava filter, deep vein thrombosis, abnormal anatomy, existing femoral access) Insufficient equipment or personnel to commence ECMO Death is deemed imminent by the treating clinician The physician deems the study is not in the patient's interest Participation or Consent is declined OR Unable to identify medical treatment decision maker.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Venovenous ECMO<br>Patients allocated to the ECMO strategy be initiated on VV ECMO and commenced on anticoagulation within <24 hours after being enrolled. Following VV ECMO initiation, the sweep gas will be gradually turned up to target a respiratory alkalosis (pH > 7.45; maximum 20% increase every 6 hours; PaCo2 < 35 mmHg), to reduce the patient's intrinsic respiratory drive. Following this, the patient will be de-sedated, and when clinically appropriate, extubated. The awake patient will be assessed daily to participate in physiotherapy: which includes sitting up, sitting out of bed, speech assessment and, where appropriate, mobilisation. | Other: Venovenous ECMO<br>* ECMO therapy for patients with hypoxic respiratory failure.<br>|
| No Intervention: Standard care<br>Patients allocated to the standard care arm will receive routine intensive care for hypoxic respiratory failure, including mechanical ventilation with a lung protective strategy (low tidal volumes, pressures and positive end expiratory pressure titration), weaning of sedation and assessment for extubation. Patients who continue to deteriorate will be eligible for initiation of VV ECMO if they meet the ECMO to rescue lung injury in severe ARDS (EOLIA) criteria: Partial pressures of arterial oxygen (PaO2):Fraction of inspired oxygen (FiO2)<50 for 3 hours, PaO2:FiO2<80 for 6 hours, pH<7.25 with PaCO2 >60 for >6 hours. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensive Care Unit Free days to Day 60 | Days alive and free from ICU to Day 60. Day Day 0 is randomisation day, with any portion of a day is spent in an ICU counted as a day. | 60 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily sedation scores | Highest (+4 Combative) and lowest (-5 Unarousable) daily Richmond Agitation and Sedation Scores (RASS). The optimal score for early mobilisation of participants on ECMO is 0 Alert and Calm. | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intensive Care Unit, ECMO, Extracorporeal Membrane Oxygenation, Mechanical Ventilation, Early ECMO