Host Response Mediators in Coronavirus (COVID-19) Infection (ARBS CORONA I)

August 11, 2020 updated by: Jim Russell, University of British Columbia

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • Recruiting
        • University of Calgary - Foothills
      • Edmonton, Alberta, Canada
        • Recruiting
        • University of Alberta
      • Edmonton, Alberta, Canada
        • Recruiting
        • Stollery Children's Hospital
        • Contact:
          • Ari Joffe, MD
    • British Columbia
      • Surrey, British Columbia, Canada
        • Not yet recruiting
        • Surrey Memorial Hospital
        • Contact:
          • Gregory Haljan, MD
      • Vancouver, British Columbia, Canada
        • Recruiting
        • Vancouver General Hospital
        • Contact:
          • David Sweet, MD
      • Vancouver, British Columbia, Canada, V6Z1Y6
        • Recruiting
        • St Pauls Hospital
        • Principal Investigator:
          • James A Russell, MD
    • Ontario
      • Brampton, Ontario, Canada
        • Recruiting
        • William Osler Health System
      • Kingston, Ontario, Canada
        • Recruiting
        • Queens University
        • Contact:
          • David Maslove, MD
      • North York, Ontario, Canada
        • Recruiting
        • Humber River Hospital
        • Contact:
          • Nataly Farshait
      • Toronto, Ontario, Canada
        • Recruiting
        • Mount Sinai Hospital
        • Contact:
          • Allison McGeer, MD
      • Toronto, Ontario, Canada
        • Not yet recruiting
        • St Michael's Hospital
      • Toronto, Ontario, Canada
        • Not yet recruiting
        • Sunnybrook Hospital
    • Quebec
      • Montréal, Quebec, Canada
        • Recruiting
        • Jewish General Hospital
      • Montréal, Quebec, Canada
        • Recruiting
        • McGill University Health Center
      • Sherbrooke, Quebec, Canada
        • Recruiting
        • Université de Sherbrooke

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Adult hospitalized patients with confirmed COVID-19

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • None

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Other: ARBs and/or ACE inhibitors
This is an observational study only.
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.
Other: ARBs and/or ACE inhibitors
This is an observational study only.
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.
Other: ARBs and/or ACE inhibitors
This is an observational study only.
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.
Other: Usual Care
This is an observational study only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
COVID-19 WHO ordinal scale
Time Frame: 14 days
14 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Organ Dysfunction
Time Frame: 14 days
14 days
28-day mortality
Time Frame: 29 days or less (may be discharged from critical care before day 28)
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)
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)
29 days or less (may be discharged from critical care before day 28)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Collaborators

University of Pennsylvania
Wuhan University
Canadian Institutes of Health Research (CIHR)
University of Alberta
McGill University Health Centre/Research Institute of the McGill University Health Centre
University of Toronto
University of Victoria
University of Calgary
University of Ottawa
Peking Union Medical College
British Columbia Centre for Disease Control

Investigators

  • Principal Investigator: James A Russell, MD, St Paul's Hospital, Center for Heart and Lung Innovation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 17, 2020

Primary Completion (ANTICIPATED)

June 30, 2021

Study Completion (ANTICIPATED)

June 30, 2022

Study Registration Dates

First Submitted

August 11, 2020

First Submitted That Met QC Criteria

August 11, 2020

First Posted (ACTUAL)

August 12, 2020

Study Record Updates

Last Update Posted (ACTUAL)

August 12, 2020

Last Update Submitted That Met QC Criteria

August 11, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H20-00600

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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