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

Australian and New Zealand Intensive Care Research Centre

Status: Enrolling

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

Treatments: Other: Venovenous ECMO

Study type: Interventional

Funder types: Other

Identifiers

NCT05562505

ANZIC-RC/AB002 V2.0

Details and patient eligibility

About

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.

Full 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.

Enrollment: 140 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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140 participants in 2 patient groups

Venovenous ECMO

Active Comparator group

Description:

Patients allocated to the ECMO strategy be initiated on V-V ECMO and on anticoagulation (blood thinning medication to prevent clot formation) within 24 hours of being allocated into the intervention group. Anticoagulant medication to prevent clot formation will be initiated as per current local practice for each site. Sites are encouraged to use best practice ECMO management that includes de-sedation, extubation, commencement of physiotherapy and rehabilitation,

Treatment:

Other: Venovenous ECMO

Standard care

No Intervention group

Description:

Patients allocated to the standard care arm will receive routine intensive care for hypoxic respiratory failure, including mechanical ventilation as per local practices, weaning of sedation and assessment for extubation. Patients who continue to deteriorate will be eligible for initiation of V-V 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.