The REDEEM Pilot Study: A Feasibility RCT of Early ECMO in Severe Acute Respiratory Infection, Including COVID-19, WHO
Condition: Mechanical Ventilation Complication; Severe Acute Respiratory Infection; Covid19
MeSH terms: Infections; Communicable Diseases; COVID-19; Respiratory Tract Infections
Study type: Interventional

Summary: 
      Patients who are critically ill in intensive care with moderate to severe acute respiratory
      infection often require mechanical ventilation. Prolonged ventilation increases the risk of
      lung damage and other side effects as a result of long term use of sedation medications.
      Extracorporeal membrane oxygenation therapy (ECMO), is a relatively new technology that uses
      a pump to remove blood from the body and return it back to the body after adding oxygen and
      removing carbon dioxide. ECMO can be used on patients who require mechanical ventilation and
      can function without the need for ongoing mechanical ventilation, thus reducing risk of side
      effects. Participants will be randomised into either the early ECMO therapy group or will
      continue standard treatment involving mechanical ventilation.

      This pilot study aims to determine if a phase 3 Randomised Control Trial (RCT) is feasible
      for the use of early ECMO therapy to treat patients with Severe Acute Respiratory Infection
      (SARI). The success of the study will be determined by the successful recruitment of adult
      patients, that there is a difference between ECMO utilisation between groups and that there
      are no safety issues.
    

Detailed description: 
      Prolonged mechanical ventilation is standard care for SARI and is associated with long term
      functional complications: Current guidelines recommend that mechanical ventilation, including
      protective lung strategies such as low tidal volumes, low peak pressures and titrated peak
      end expiratory pressure (PEEP), should form the mainstay of treatment for severe respiratory
      failure. While these strategies have been shown to reduce mortality, the application of
      invasive mechanical ventilation in the setting of SARIs may in fact propagate ongoing lung
      injury. Ventilator induced lung injury (VILI) results from the high pressures, over
      distension, and shear injury used by the ventilator to maintain gas exchange. Invasive
      ventilation can lead to secondary bacterial infection from poor clearance of sputum by
      sedated patients. And "air hunger" - the rapid and deep injurious breathing pattern by
      patients with severe lung injury - can lead to patient self-induced lung injury (P-SILI).
      Taken together, these factors can lead to a vicious cycle - the VILI Vortex - where lung
      damage leads to shrinkage of the functional lung unit, reduced compliance, higher
      transpulmonary pressures, worsening inflammation, further shrinkage, and ultimately even more
      severe lung damage and gas exchange failure.

      Current strategies to facilitate mechanical ventilation include prolonged heavy sedation to
      assist patient-ventilator synchronization, and neuromuscular blockade (to prevent any
      spontaneous respiratory effort), often for weeks at a time. These interventions, plus the
      underlying lung damage, contribute to significant long term complications, including
      immobility and ICU myopathy, delirium, respiratory muscle weakness and tracheostomy, leading
      to significant delays in ICU and hospital discharge, rehabilitation, and return to home.
      Survivors of prolonged mechanical ventilation have been shown to have high rates of
      functional disability, immobility, psychological injury, and reduced health related quality
      of life - and these outcomes can persist for up to 5 years.

      Thus, conventional treatment with mechanical ventilation, deep sedation, and/or neuromuscular
      paralysis is likely to adversely impact long term functional outcomes in patients with SARI.
      There is a clear unmet need for novel strategies that facilitate safe lung ventilation, while
      also limiting the intensity and duration of these interventions and complications.

      ECMO is an external machine that oxygenates the blood in addition to a mechanical ventilator.
      Venous cannulae drain blood out of the body and return it back after an oxygenator adds
      oxygen and removes carbon dioxide. Venovenous (VV) ECMO supports patients with respiratory
      failure, by providing the body with sufficient oxygen and by removing all the carbon dioxide
      (CO2) in the blood (causing a respiratory alkalosis), which reduces the drive to breathe and
      permits "lung rest". Resting the lungs avoids VILI, reduces pulmonary and systemic
      inflammation, and reduces extra-pulmonary organ dysfunction. Traditionally, ECMO was employed
      very late in the course of the disease as a "rescue therapy", when patients already had
      severely damaged lungs, due to fears of complications such as bleeding that would worsen the
      patients multi organ failure. However advances in modern ECMO technology mean it is
      associated with a lower complication rate (<10% cannula site bleeding) and its use has
      doubled over the last five years. ECMO now offers the ideal platform to prevent
      ventilator-induced lung damage in patients that are less severely unwell, and earlier in the
      disease process, while also reducing the need for heavy sedation and/or neuromuscular
      blockade. It facilitates safe de-sedation without VILI as well as extubation, and
      physiotherapy-which is difficult to carry out adequately when a patient is sedated and
      ventilated. All these factors have been associated with improved long term health outcomes
      for patients.

      This study aims to determine if a large RCT looking at use of early ECMO to treat patients
      with SARI is feasible.
    

Intervention name(s): VV-ECMO
Intervention type(s): Other
Intervention description(s): Early use of VV-ECMO in SARI patients.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Intensive Care Unit; ECMO; Extracorporeal membrane oxygenation; Mechanical ventilation; Early ECMO