Clinical trial NCT05562505: Trial of Venovenous ECMO to De-Sedate, Extubate and Mobilise in Hypoxic Respiratory Failure
Official title: A Randomised Controlled Trial of Venovenous ECMO to De-Sedate, Extubate and Mobilise in Hypoxic Respiratory Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mechanical Ventilation Complication
Hypoxemia
Acute Respiratory Distress Syndrome Due to COVID-19
COVID-19 Respiratory Infection
Pneumonia
Extracorporeal Membrane Oxygenation
Keywords: Intensive Care Unit
ECMO
Extracorporeal Membrane Oxygenation
Mechanical Ventilation
Early ECMO
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
Collaborators: name: The Alfred
First posted: 2022-09-30
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients ≥18 to 65 years old
2. Acute hypoxemic respiratory failure characterised by new or worsening respiratory symptoms developing within 2 weeks prior to the onset of need for oxygen or respiratory support
3. Mechanical ventilation of \<7 days
4. Moderate to severe respiratory failure, as demonstrated by two P:F ratios \<150mmHg at least 6 hours apart. Arterial Blood Gases (ABG) with P:F ratio \> 150mmHg are permitted between the two trial inclusion ABGs.
5. Trial of proning (unless contraindicated)

Exclusion Criteria:

1. The patient will be extubated today or tomorrow (i.e. will not remain intubated and ventilated the day after tomorrow)
2. Cardiogenic cause of respiratory failure
3. Chronic hypercapnic respiratory failure defined as PaCO2 \> 60 mmHg in the outpatient setting
4. Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep disordered breathing
5. Confirmed diffuse alveolar haemorrhage from vasculitis
6. Neurologic conditions, i.e. undergoing treatment for intracranial hypertension
7. Currently receiving any form of ECMO (e.g., venovenous, venoarterial, or hybrid configuration)
8. Patient needing immediate VV ECMO (as per EOLIA criteria)
9. The patient is moribund and deemed unlikely to survive past 24 hours (as determined by the clinical team)
10. The patient is being transitioned to palliative care
11. Contraindications to anticoagulation (e.g., active GI bleeding, bleeding predisposition, severe trauma)
12. Previous hypersensitivity/anaphylactic reaction to heparin or heparin-induced thrombocytopenia
13. Participation or Consent is declined, OR
14. Unable to identify or Contact surrogate decision maker.

Primary outcomes:
measure: Intensive Care Unit Free days to Day 60
timeFrame: 60 Days
Secondary outcomes:
measure: Daily sedation scores
timeFrame: Day 28
Other outcomes:
measure: Extubation rates
timeFrame: Day 28
measure: Participation in early mobilisation
timeFrame: Day 28
measure: Number of Participants who were randomised to standard care initially and subsequently needed VV-ECMO.
timeFrame: Day 28
measure: WHO Disability Assessment Schedule 2.0 (WHODAS 2.0)
timeFrame: Day 180
measure: EuroQol EQ5D-5L
timeFrame: Day 180
Locations:
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred
state: New South Wales
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Perth
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Berlin
country: Germany
facility: Charite Universitatmedizin
Study officials:
affiliation: Monash University
name: Aidan Burrell, MBBS
role: PRINCIPAL_INVESTIGATOR
References: