Can RIC Prevent Deterioration to Critical Care in Covid19
Condition: Covid19; Ischemia
MeSH terms: COVID-19; Ischemia
Study type: Interventional

Summary: 
      The coronavirus disease (COVID-19) emerged in late 2019 and has since been diagnosed in over
      a million persons worldwide. As this virus progresses, it causes an extreme and uncontrolled
      response from the patient's immune system accompanied by reduced oxygen flow to major organs,
      and subsequent ischaemic injury.

      The current treatment of COVID-19 is largely supportive without any cure or vaccine available
      at this time. Developing new methods to reduce this heightened inflammatory response is
      essential to halting progression of COVID-19 in patients and reducing the severity of damage.

      The cellular mechanisms seen in COVID-19 are similar to those seen in patients with sepsis. A
      process known as Remote Ischemic Conditioning (RIC) is an intervention which has been shown
      to prevent cellular injury including those associated with sepsis. Based on the evidence from
      studies looking at sepsis, it is anticipated the same benefit would be seen in patients
      diagnosed with COVID-19.

      RIC is a simple, non-invasive procedure where a blood pressure cuff is applied to the arm for
      repeated cycles of inflating and deflating (typically 3-5 cycles of 5 minutes each). This
      process activates pro-survival mechanisms in the body to protect vital organs and improve the
      immune system. Therefore, we believe it represents an exciting strategy to protect organs
      against reduced blood flow and extreme immune response, as seen in COVID-19 infections.

      This study has already been fully approved
    

Detailed description: 
      COVID-19 has an early phase and a late, with rapid progression to ARDS (due to cytokine
      storm), multi-organ failure and death. Suppressing these cytokine elevations maybe a key to
      improved outcomes. Acute and Chronic (repeated) RIC has been shown to benefit in reducing the
      levels cytokines following LPS-induced sepsis in animal models (1). Furthermore, mortality
      was significantly reduced, following chronic RIC administration as opposed to acute RIC
      administration.

      RIC in COVID-19 patients is a pilot, multi-centre, randomised study, designed to ascertain
      whether RIC decreases the severity of inflammatory markers associated with a "storm" score.

      20 adult patients admitted to either The Royal Free or The Lister Hospital (Stevenage) with
      diagnosed COVID-19 will be enrolled into the study, of confirmed but not critical status.
      After enrolment, patients will be randomised (n = 10 per group) 1:1 to receive RIC or no
      adjunctive intervention.

      RIC will consist of 3-4 cycles of cuff inflations to 200 mmHg for 5 min with deflation to 0
      mmHg for another 5 min, which is automatically administered by the pre-programmed cuff. Those
      randomised to the control group will have the blood pressure cuff placed on the arm, but it
      will not be inflated. RIC will be performed daily for 15 days.

      Venous blood will be collected following RIC administration (where possible) and saved for
      the subsequent measurement of inflammatory markers such as TNF, IL-1β, IL-6, and HMGB1 in
      addition to cardiac biomarkers Troponin T and NT pro terminal BNP. All biomarker analysis
      will occur at The Hatter Cardiovascular Institute, UCL.

      The endpoint is area under the curve of inflammatory markers and cardiac biomarkers.
      Secondary endpoint will be the need for intensive care admission or death.

      It would be our intention to use autoRIC devices (CellAegis, Canada) to ascertain whether RIC
      can lower the cytokine response. These devices are specifically designed, blood-pressure
      cuffs pre-programmed for the number of uses required by each patient; the intent being "a
      single patient-multiple use" cuff.
    

Intervention name(s): Cuff application with inflation; Sham inflation
Intervention type(s): Procedure; Other
Intervention description(s): The blood pressure cuff will be placed on the arm and inflated.; The blood pressure cuff will be placed on the arm and not inflated.
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Covid19; Ischemia