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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pneumonia; Extracorporeal Membrane Oxygenation; Mechanical Ventilation Complication; Hypoxemia; COVID-19 Respiratory Infection; Acute Respiratory Distress Syndrome Due to COVID-19
• Intervention / Treatment: Other: Venovenous ECMO

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephanie M Hunter; Phone Number: +61 3 9903 0646; Email: Stephanie.Hunter@monash.edu
• Study Contact Backup: Name: Tony Trapani; Phone Number: +61 3 9903 0343; Email: tony.trapani@monash.edu

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent'S Hospital Sydney
    • Sydney, New South Wales, Australia
      • Royal Prince Alfred
  • Queensland
    • Brisbane, Queensland, Australia
      • The Prince Charles Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Germany
  • Berlin, Germany, 10117
    • Charite Universitatmedizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Venovenous ECMO; 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; ECMO therapy for patients with hypoxic respiratory failure.
No Intervention: Standard care; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extubation rates	Date and time of enduring extubation	Day 28
Participation in early mobilisation	Daily assessment for mobilisation by allied health clinicians using the ICU Mobility Scale. The ICU Mobility Scale ranges from 0-Lying in Bed, to 10-Walking Independently without a Gait Aid. Score 7-Walking With the Assistance of 2 or More People is the best outcome achievable for participants on ECMO.	Day 28
Number of Participants who were randomised to standard care initially and subsequently needed VV-ECMO.	Number of Participants who were randomised to standard care initially and subsequently needed VV-ECMO.	Day 28
WHO Disability Assessment Schedule 2.0 (WHODAS 2.0)	Assessment of 6 domains of functioning for participants at Day 180 follow up via telephone interview. Total possible scores are 48. A lower score indicates a better outcome.	Day 180
EuroQol EQ5D-5L	Health-related quality of life reported via telephone interview at Day 180 using the EuroQol EQ5D. Total possible scores are 25. A lower score indicates a better outcome.	Day 180

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre
• Collaborators: The Alfred
• Investigators: Principal Investigator: Aidan Burrell, MBBS, Monash University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2022
• Primary Completion (Anticipated): July 31, 2026
• Study Completion (Anticipated): January 31, 2027

Study Registration Dates

• First Submitted: September 11, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 30, 2022

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Intensive Care Unit; ECMO; Mechanical Ventilation; Extracorporeal Membrane Oxygenation; Early ECMO
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Signs and Symptoms, Respiratory; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Insufficiency; Respiratory Tract Infections; Hypoxia; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: ANZIC-RC/AB002 V2.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The Management Committee support the view of the International Committee of Medical Journal Editors and the World Health Organisation (WHO) with reference to the ethical obligation to responsibly share data acquired by interventional clinical trials. At the conclusion of the study, the management committee will consider requests from researchers who provide a methodically sound scientific proposal as per the Data Sharing Policy set out in the Australian and New Zealand Intensive Care Research Centre (ANZIC-RC) Terms of Reference. Only de-identified data will be shared and all requests for data must comply with the ethical, regulatory, and legislative requirements governing their jurisdiction.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No