Covid19NCT04699227
Can RIC Prevent Deterioration to Critical Care in Covid19
A study testing Cuff application with inflation in people with Covid19 and Ischemia, run by Derek Yellon at 4 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- What is being tested?
- Cuff application with inflation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 15 Jan 2021to 31 Oct 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (aged 18 - 80 yrs) with diagnosed COVID-19.
Who cannot join
- 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
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United Kingdom2 sites
Royal Free London NHS Foundation Trust,
London, NW3 2QG
East and North Hertfordshire NHS TrusEast and North Hertfordshire NHS Trus
Stevenage, SG1 4AB
Brazil1 site
Atherosclerosis and Vascular Biology laboratory, State University of Campinas
Campinas
South Africa1 site
Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town
Cape Town
About this study
Official title: CAN REMOTE ISCHAEMIC CONDITIONING REDUCE INFLAMMATORY MARKERS IN COVID-19 PATIENTS - A MULTI-SITE, RANDOMISED PILOT STUDY
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.
Read more
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
Read the 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.
- Being tested
- Cuff application with inflation, Sham inflation
- Keywords
- Covid19, Ischemia
- Medical subject headings
- COVID-19, Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cuff application with inflationProcedure or surgery
The blood pressure cuff will be placed on the arm and inflated.
Sham inflationOther
The blood pressure cuff will be placed on the arm and not inflated.
| Study group | Role | What they receive |
|---|---|---|
| Control group not receiving RIC | Sham comparator | Those randomised to the control group will have the blood pressure cuff placed on the arm, but it will not be inflated. Receives: Other: Sham inflation |
| Interventional group receiving RIC | Experimental | 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. Receives: Procedure: Cuff application with inflation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Endpoint
The primary outcome is to demonstrate that remote ischaemic conditioning reduces the severity of inflammatory cytokine release which are responsible for the cytokine "storm" that occurs in following COVID-19 infection.
The endpoint is area under the curve of inflammatory markers and cardiac biomarkers.
Measured: 12 months
Secondary outcomes (1)
Secondary Endpoint
Secondary endpoint will be the need for intensive care admission or death.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2021
- Study start15 Jan 2021
- Primary completion31 Aug 2021
- Study completion31 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Derek Yellon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Derek Yellon, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04699227
- Sponsor's protocol ID
- 20/SC/0192
- Status last verified
- Nov 2023
- First submitted
- 6 Jan 2021
- Last updated
- 29 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No identifiable, personal data will be collected as part of this study.
Publications
Lukhna K, do Carmo HRP, Castillo AR, Davidson SM, Geffen H, Giesz S, Golforoush P, Bovi TG, Gorag D, Salama A, Imamdin A, Kalkhoran S, Lecour S, Perroud MW Jr, Ntsekhe M, Sposito AC, Yellon DM. Effect of Remote Ischaemic Conditioning on the Inflammatory Cytokine Cascade of COVID-19 (RIC in COVID-19): a Randomized Controlled Trial. Cardiovasc Drugs Ther. 2024 Jun;38(3):433-445. doi: 10.1007/s10557-022-07411-2. Epub 2022 Nov 29.
PubMed 36445625Davidson SM, Lukhna K, Gorog DA, Salama AD, Castillo AR, Giesz S, Golforoush P, Kalkhoran SB, Lecour S, Imamdin A, do Carmo HRP, Bovi TG, Perroud MW Jr, Ntsekhe M, Sposito AC, Yellon DM. RIC in COVID-19-a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19. Cardiovasc Drugs Ther. 2022 Oct;36(5):925-930. doi: 10.1007/s10557-021-07221-y. Epub 2021 Jun 25.
PubMed 34169381
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CAN REMOTE ISCHAEMIC CONDITIONING REDUCE INFLAMMATORY MARKERS IN COVID-19 PATIENTS - A MULTI-SITE, RANDOMISED PILOT STUDY
- ClinicalTrials.gov ID
- NCT04699227
- Acronym / sponsor ID
- 20/SC/0192
- Keywords
- Covid19, Ischemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Derek YellonUniversity, hospital or other
- Study start
- 15 Jan 2021 (actual)
- Primary completion
- 31 Aug 2021 (actual)
- Study completion
- 31 Oct 2021 (actual)
- First posted
- 7 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group not receiving RIC | Sham comparator | Other: Sham inflationThose randomised to the control group will have the blood pressure cuff placed on the arm, but it will not be inflated. |
| Interventional group receiving RIC | Experimental | Procedure: Cuff application with inflationRIC 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients (aged 18 - 80 yrs) with diagnosed COVID-19.
Key exclusion criteria (4 listed)
- 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 is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cuff application with inflationThe blood pressure cuff will be placed on the arm and inflated. | Procedure or surgery | Interventional group receiving RIC |
| Sham inflationThe blood pressure cuff will be placed on the arm and not inflated. | Other | Control group not receiving RIC |
Primary outcome
Primary Endpoint
Time frame: 12 months
The primary outcome is to demonstrate that remote ischaemic conditioning reduces the severity of inflammatory cytokine release which are responsible for the cytokine "storm" that occurs in following COVID-19 infection. The endpoint is area under the curve of inflammatory markers and cardiac biomarkers.
1 secondary outcome
Secondary Endpoint
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Derived from this study: PubMed 36445625Lukhna K, do Carmo HRP, Castillo AR, Davidson SM, Geffen H, Giesz S, Golforoush P, Bovi TG, Gorag D, Salama A, Imamdin A, Kalkhoran S, Lecour S, Perroud MW Jr, Ntsekhe M, Sposito AC, Yellon DM. Effect of Remote Ischaemic Conditioning on the Inflammatory Cytokine Cascade of COVID-19 (RIC in COVID-19): a Randomized Controlled Trial. Cardiovasc Drugs Ther. 2024 Jun;38(3):433-445. doi: 10.1007/s10557-022-07411-2. Epub 2022 Nov 29.
- Derived from this study: PubMed 34169381Davidson SM, Lukhna K, Gorog DA, Salama AD, Castillo AR, Giesz S, Golforoush P, Kalkhoran SB, Lecour S, Imamdin A, do Carmo HRP, Bovi TG, Perroud MW Jr, Ntsekhe M, Sposito AC, Yellon DM. RIC in COVID-19-a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19. Cardiovasc Drugs Ther. 2022 Oct;36(5):925-930. doi: 10.1007/s10557-021-07221-y. Epub 2021 Jun 25.
- Individual participant dataSharing planned: No. No identifiable, personal data will be collected as part of this study.
Related trials for Covid19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cuff application with inflation in people with Covid19 and Ischemia, run by Derek Yellon at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom, Brazil, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Endpoint (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04699227, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2023.