COVID-19ARBS CORONA INCT04510623
Host Response Mediators in Coronavirus (COVID-19) Infection
An observational study of COVID-19 and SARS-CoV2, run by University of British Columbia at 15 sites in Canada.
Trial summary
The coronavirus (COVID-19) pandemic continues to grow exponentially. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- ARBs and/or ACE inhibitors
- How many people
- 500 participants
- Where
- 15 sitesCanada
- Study dates
- 17 Mar 2020to 30 Jun 2022
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult hospitalized patients with confirmed COVID-19
Who may be able to join
- Individuals over 18 years of age who have confirmed COVID-19 infection (according to local hospital or provincial laboratories clinically approved laboratory testing for COVID-19).
Who cannot join
- None
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Canada15 sites, 15 recruiting
- Recruiting
William Osler Health System
Brampton, Ontario
- Recruiting
University of Calgary - Foothills
Calgary, Alberta
Brent Winston, MD
- Recruiting
Stollery Children's Hospital
Edmonton, Alberta
Ari Joffe, MD
- Recruiting
University of Alberta
Edmonton, Alberta
Oleksa Rewa, MD
- Recruiting
Queens University
Kingston, Ontario
David Maslove, MD
- Recruiting
Jewish General Hospital
Montreal, Quebec
Todd Lee, MD
- Recruiting
McGill University Health Center
Montreal, Quebec
Matthew Cheng, MD
- Recruiting
Humber River Hospital
North York, Ontario
Nataly Farshait
- Recruiting
Université de Sherbrooke
Sherbrooke, Quebec
Francois Lamontagne, MD
- Not yet recruiting
Surrey Memorial Hospital
Surrey, British Columbia
Gregory Haljan, MD
- Recruiting
Mount Sinai Hospital
Toronto, Ontario
Allison McGeer, MD
- Not yet recruiting
St Michael's Hospital
Toronto, Ontario
John Marshall, MD
- Not yet recruiting
Sunnybrook Hospital
Toronto, Ontario
Robert Fowler, MD
- Recruiting
St Pauls Hospital
Vancouver, British Columbia, V6Z1Y6
Puneet Mann, MSc, 604 682 2344 ext. 64734, pmann7@providencehealth.bc.ca
James A Russell, MD
- Recruiting
Vancouver General Hospital
Vancouver, British Columbia
David Sweet, MD
About this study
Official title: Host Response Mediators in Coronavirus (COVID-19) Infection - Is There a Protective Effect of Angiotensin II Type 1 Receptor Blockers (ARBs) on Outcomes of Coronavirus Infection?
The coronavirus (COVID-19) pandemic continues to grow exponentially. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Preliminary data shows angiotensin II receptor blockers (ARBs) limits lung injury in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and organ injury in COVID-19. We will therefore collect clinical chart data and test angiotensin II levels of patients who are admitted to ICU with COVID-19 to determine whether there is a correlation between taking ARBs and clinical outcomes in these patients.
Other blood biomarkers and clinical risk factors for COVID-19 have come to light in recent weeks. We include these in our observational analysis to help generate an understanding of COVID-19 presentation and blood biomarker characterization of disease.
Read the detailed description
Purpose: To determine whether angiotensin II receptor blockers (ARBs) decrease severity or mortality in hospitalized COVID-19 infected adults.
Main Hypothesis: Modulation of ACE2 by ARBs decreases the need for hospitalization, severity (need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement therapy) or mortality of hospitalized COVID-19 infected adults.
Secondary Hypotheses:
- Plasma angiotensin I and II and other biomarker levels are associated with effectiveness of ARBs in hospitalized COVID-19 adults
- Modulation of ACE2 by angiotensin type I receptor blockers is associated with decreased rate of hospitalization for COVID-19
- In patients already on ARBs when they are hospitalized continuing ARBs is associated with decreased World Health Organization (WHO) COVID-19 ordinal outcome scale
Justification: The COVID-19 epidemic continues to grow exponentially affecting over 71,429 individuals with 1775 deaths (February 17, 2020), mostly in China but also in other countries. The population mortality rate is 2% (lower than SARS (10%) and MERS (36%) but is 10% in hospitalized and 24% in ICU-admitted COVID-19 patients in China. Recent data from China (not yet public domain) suggest ICU mortality is higher (J. Marshall personal communication). Interventions to date include quarantine, isolation and usual clinical care. There are no proven antiviral or host modulating interventions for COVID-19. Notably, critically ill COVID-19 patients have similar mortality rates as sepsis and acute respiratory distress syndrome. Cohort studies have shown that patients already on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have lower sepsis mortality. Angiotensin II worsens lung injury in influenza models because ACE2 is downregulated in H1N1, H5N1, H7N9, and SARS viral infections leading to increased angiotensin II. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Preliminary data shows ARBs limits lung injury in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and organ injury in COVID-19.
Research Design:
Prospective clinical chart review: we will collect clinical data on the participant throughout their hospital stay. Includes collection of baseline characteristics such as age, sex, heart rate, respiratory rate, temperature, blood pressure, SaO2, respiratory (PaO2/FiO2), renal (creatinine) and hepatic (bilirubin) function, use of oxygen, vasopressors, ventilation and RRT. They will be followed daily throughout their hospital stay, until death or discharge. Using left over clinical blood collected upon admission to hospital, plasma angiotensin I and II and other biomarker levels will be measured in our research laboratories.
- Being tested
- ARBs and/or ACE inhibitors, Usual Care
- Keywords
- ARBs, angiotensin II type 1 receptor blocker, ACEi, acute respiratory distress syndrome, COVID-19, coronavirus, Multisite, Canada, Observational, acute kidney injury, shock
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome, Coronavirus Infections, Acute Kidney Injury, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARBs and/or ACE inhibitorsOther
This is an observational study only.
Usual CareOther
This is an observational study only.
| Study group | Role | What they receive |
|---|---|---|
| COVID-19 Patients on ARBs | This is an observational cohort study. Those who have COVID-19 in hospital and are on Angiotensin Receptor Blockers will be included in this cohort. Receives: Other: ARBs and/or ACE inhibitors | |
| COVID-19 Patients on ACE inhibitors | This is an observational cohort study. Those who have COVID-19 in hospital and are on Angiotensin-Converting Enzyme inhibitors will be included in this cohort. Receives: Other: ARBs and/or ACE inhibitors | |
| COVID-19 Patients on ARBs or ACE inhibitors | This is an observational cohort study. Those who have COVID-19 in hospital and are on ARBs or ACEi's will be included in this cohort. Receives: Other: ARBs and/or ACE inhibitors | |
| COVID-19 Patients not on ARBs or ACE inhibitors | This is an observational cohort study. Those who have COVID-19 in hospital and are not on ARBs or ACEi's will be included in this cohort. Receives: Other: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
COVID-19 WHO ordinal scale
Measured: 14 days
Secondary outcomes (4)
Organ Dysfunction
Measured: 14 days
28-day mortality
Measured: 29 days or less (may be discharged from critical care before day 28)
Hospital/ICU length of stay
Measured: 29 days or less (may be discharged before day 28)
ICU admission
Measured: 29 days or less (may be discharged from critical care before day 28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2020
- Study start17 Mar 2020
- Primary completion30 Jun 2021 (estimated)
- Study completion30 Jun 2022 (estimated)
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 COVID-19Studies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), British Columbia Centre for Disease Control, McGill University Health Centre/Research Institute of the McGill University Health Centre, University of Toronto, University of Ottawa, University of Calgary, University of Alberta, University of Victoria, Wuhan University, Peking Union Medical College, University of Pennsylvania
- Responsible party
- Principal investigator, Jim Russell, University of British Columbia
- Investigators
- James A Russell, MD, Principal investigator, St Paul's Hospital, Center for Heart and Lung Innovation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04510623
- Sponsor's protocol ID
- H20-00600
- Acronym
- ARBS CORONA I
- Status last verified
- Aug 2020
- First submitted
- 11 Aug 2020
- Last updated
- 12 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lee T, Cheng MP, Vinh DC, Lee TC, Tran KC, Winston BW, Sweet D, Boyd JH, Walley KR, Haljan G, McGeer A, Lamontagne F, Fowler R, Maslove D, Singer J, Patrick DM, Marshall JC, Burns KD, Murthy S, Mann PK, Hernandez G, Donohoe K, Rocheleau G, Russell JA; ARBs CORONA I study investigators. Organ dysfunction and death in patients admitted to hospital with COVID-19 in pandemic waves 1 to 3 in British Columbia, Ontario and Quebec, Canada: a cohort study. CMAJ Open. 2022 Apr 19;10(2):E379-E389. doi: 10.9778/cmajo.20210216. Print 2022 Apr-Jun.
PubMed 35440485Russell JA, Marshall JC, Slutsky A, Murthy S, Sweet D, Lee T, Singer J, Patrick DM, Du B, Peng Z, Cheng M, Burns KD, Harhay MO. Study protocol for a multicentre, prospective cohort study of the association of angiotensin II type 1 receptor blockers on outcomes of coronavirus infection. BMJ Open. 2020 Dec 7;10(12):e040768. doi: 10.1136/bmjopen-2020-040768.
PubMed 33293316
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Host Response Mediators in Coronavirus (COVID-19) Infection - Is There a Protective Effect of Angiotensin II Type 1 Receptor Blockers (ARBs) on Outcomes of Coronavirus Infection?
- ClinicalTrials.gov ID
- NCT04510623
- Acronym / sponsor ID
- ARBS CORONA I / H20-00600
- Keywords
- ARBs, angiotensin II type 1 receptor blocker, ACEi, acute respiratory distress syndrome, COVID-19, coronavirus, Multisite, Canada
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), British Columbia Centre for Disease Control, McGill University Health Centre/Research Institute of the McGill University Health Centre, University of Toronto, University of Ottawa, University of Calgary, University of Alberta, University of Victoria, Wuhan University, Peking Union Medical College, University of Pennsylvania
- Study start
- 17 Mar 2020 (actual)
- Primary completion
- 30 Jun 2021 (estimated)
- Study completion
- 30 Jun 2022 (estimated)
- First posted
- 12 Aug 2020 (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 (COVID-19) pandemic continues to grow exponentially. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Preliminary data shows angiotensin II receptor blockers (ARBs) limits lung injury in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and organ injury in COVID-19. We will therefore collect clinical chart data and test angiotensin II levels of patients who are admitted to ICU with COVID-19 to determine whether there is a correlation between taking ARBs and clinical outcomes in these patients.
Other blood biomarkers and clinical risk factors for COVID-19 have come to light in recent weeks. We include these in our observational analysis to help generate an understanding of COVID-19 presentation and blood biomarker characterization of disease.
Detailed description
Purpose: To determine whether angiotensin II receptor blockers (ARBs) decrease severity or mortality in hospitalized COVID-19 infected adults.
Main Hypothesis: Modulation of ACE2 by ARBs decreases the need for hospitalization, severity (need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement therapy) or mortality of hospitalized COVID-19 infected adults.
Secondary Hypotheses:
- Plasma angiotensin I and II and other biomarker levels are associated with effectiveness of ARBs in hospitalized COVID-19 adults
- Modulation of ACE2 by angiotensin type I receptor blockers is associated with decreased rate of hospitalization for COVID-19
- In patients already on ARBs when they are hospitalized continuing ARBs is associated with decreased World Health Organization (WHO) COVID-19 ordinal outcome scale
Justification: The COVID-19 epidemic continues to grow exponentially affecting over 71,429 individuals with 1775 deaths (February 17, 2020), mostly in China but also in other countries. The population mortality rate is 2% (lower than SARS (10%) and MERS (36%) but is 10% in hospitalized and 24% in ICU-admitted COVID-19 patients in China. Recent data from China (not yet public domain) suggest ICU mortality is higher (J. Marshall personal communication). Interventions to date include quarantine, isolation and usual clinical care. There are no proven antiviral or host modulating interventions for COVID-19. Notably, critically ill COVID-19 patients have similar mortality rates as sepsis and acute respiratory distress syndrome. Cohort studies have shown that patients already on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have lower sepsis mortality. Angiotensin II worsens lung injury in influenza models because ACE2 is downregulated in H1N1, H5N1, H7N9, and SARS viral infections leading to increased angiotensin II. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Preliminary data shows ARBs limits lung injury in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and organ injury in COVID-19.
Research Design:
Prospective clinical chart review: we will collect clinical data on the participant throughout their hospital stay. Includes collection of baseline characteristics such as age, sex, heart rate, respiratory rate, temperature, blood pressure, SaO2, respiratory (PaO2/FiO2), renal (creatinine) and hepatic (bilirubin) function, use of oxygen, vasopressors, ventilation and RRT. They will be followed daily throughout their hospital stay, until death or discharge. Using left over clinical blood collected upon admission to hospital, plasma angiotensin I and II and other biomarker levels will be measured in our research laboratories.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| COVID-19 Patients on ARBs | – | Other: ARBs and/or ACE inhibitorsThis is an observational cohort study. Those who have COVID-19 in hospital and are on Angiotensin Receptor Blockers will be included in this cohort. |
| COVID-19 Patients on ACE inhibitors | – | Other: ARBs and/or ACE inhibitorsThis is an observational cohort study. Those who have COVID-19 in hospital and are on Angiotensin-Converting Enzyme inhibitors will be included in this cohort. |
| COVID-19 Patients on ARBs or ACE inhibitors | – | Other: ARBs and/or ACE inhibitorsThis is an observational cohort study. Those who have COVID-19 in hospital and are on ARBs or ACEi's will be included in this cohort. |
| COVID-19 Patients not on ARBs or ACE inhibitors | – | Other: Usual CareThis is an observational cohort study. Those who have COVID-19 in hospital and are not on ARBs or ACEi's will be included in this cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult hospitalized patients with confirmed COVID-19
Key inclusion criteria (1 listed)
- Individuals over 18 years of age who have confirmed COVID-19 infection (according to local hospital or provincial laboratories clinically approved laboratory testing for COVID-19).
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| ARBs and/or ACE inhibitorsThis is an observational study only. | Other | COVID-19 Patients on ACE inhibitors, COVID-19 Patients on ARBs, COVID-19 Patients on ARBs or ACE inhibitors |
| Usual CareThis is an observational study only. | Other | COVID-19 Patients not on ARBs or ACE inhibitors |
Primary outcome
COVID-19 WHO ordinal scale
Time frame: 14 days
4 secondary outcomes
Organ Dysfunction
Time frame: 14 days
28-day mortality
Time frame: 29 days or less (may be discharged from critical care before day 28)
Hospital/ICU length of stay
Time frame: 29 days or less (may be discharged before day 28)
ICU admission
Time frame: 29 days or less (may be discharged from critical care before day 28)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2020.
- Derived from this study: PubMed 35440485Lee T, Cheng MP, Vinh DC, Lee TC, Tran KC, Winston BW, Sweet D, Boyd JH, Walley KR, Haljan G, McGeer A, Lamontagne F, Fowler R, Maslove D, Singer J, Patrick DM, Marshall JC, Burns KD, Murthy S, Mann PK, Hernandez G, Donohoe K, Rocheleau G, Russell JA; ARBs CORONA I study investigators. Organ dysfunction and death in patients admitted to hospital with COVID-19 in pandemic waves 1 to 3 in British Columbia, Ontario and Quebec, Canada: a cohort study. CMAJ Open. 2022 Apr 19;10(2):E379-E389. doi: 10.9778/cmajo.20210216. Print 2022 Apr-Jun.
- Derived from this study: PubMed 33293316Russell JA, Marshall JC, Slutsky A, Murthy S, Sweet D, Lee T, Singer J, Patrick DM, Du B, Peng Z, Cheng M, Burns KD, Harhay MO. Study protocol for a multicentre, prospective cohort study of the association of angiotensin II type 1 receptor blockers on outcomes of coronavirus infection. BMJ Open. 2020 Dec 7;10(12):e040768. doi: 10.1136/bmjopen-2020-040768.
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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.
James A Russell, MD principal investigator
St Paul's Hospital, Center for Heart and Lung Innovation
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 and SARS-CoV2, run by University of British Columbia at 15 sites in Canada.
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 1 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: status not confirmed, as of the sponsor's last update on 12 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Canada. 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Puneet Mann, MSc (604 682 2344 ext. 64734, pmann7@providencehealth.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
COVID-19 WHO ordinal scale (time frame: 14 days). 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 NCT04510623, 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 12 Aug 2020.