Official Title
CAN REMOTE ISCHAEMIC CONDITIONING REDUCE INFLAMMATORY MARKERS IN COVID-19 PATIENTS - A MULTI-SITE, RANDOMISED PILOT STUDY
Brief 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.

Recruiting
COVID19
Ischemia

Procedure: Cuff application with inflation

The blood pressure cuff will be placed on the arm and inflated.

Other: Sham inflation

The blood pressure cuff will be placed on the arm and not inflated.

Eligibility Criteria

Inclusion Criteria:

- Adult patients (aged 18 - 80 yrs) with diagnosed COVID-19.

Exclusion Criteria:

- Contraindication for the use of a brachial cuff on either arm.

- Intercurrent disease with an expected life expectancy of less than 24 h, cardiac
arrest, - Pregnant or breastfeeding women.

- Bleeding disorder or platelet count below 50.

- Currently enrolled in another research study

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 80 Years
Countries
Brazil
South Africa
United Kingdom
Locations

Atherosclerosis and Vascular Biology laboratory, State University of Campinas
Campinas, Brazil

Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town
Cape Town, South Africa

Royal Free London NHS Foundation Trust,
London, United Kingdom

East and North Hertfordshire NHS TrusEast and North Hertfordshire NHS Trus
Stevenage, United Kingdom

NCT Number
Keywords
COVID19
Ischemia
MeSH Terms
COVID-19
Ischemia