Host Response Mediators in Coronavirus (COVID-19) Infection

COVID-19 Clinical Trial

— ARBS CORONA I  

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?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04510623
• Other study ID #: H20-00600
• Status: Recruiting
• Start date: March 17, 2020
• Est. completion date: June 30, 2022

Study information

• Verified date: August 2020
• Source: University of British Columbia
• Contact: Puneet Mann, MSc
• Phone: 604 682 2344
• Email: pmann7[@]providencehealth.bc.ca
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Infections
• COVID-19
• SARS-CoV2

Intervention

Other:
• ARBs and/or ACE inhibitors
This is an observational study only.
• Usual Care
This is an observational study only.

Locations

Country	Name	City	State
Canada	William Osler Health System	Brampton	Ontario
Canada	University of Calgary - Foothills	Calgary	Alberta
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Queens University	Kingston	Ontario
Canada	Jewish General Hospital	Montréal	Quebec
Canada	McGill University Health Center	Montréal	Quebec
Canada	Humber River Hospital	North York	Ontario
Canada	Université de Sherbrooke	Sherbrooke	Quebec
Canada	Surrey Memorial Hospital	Surrey	British Columbia
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	St Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Hospital	Toronto	Ontario
Canada	St Pauls Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia

Sponsors (12)

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

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	COVID-19 WHO ordinal scale		14 days
Secondary	Organ Dysfunction		14 days
Secondary	28-day mortality		29 days or less (may be discharged from critical care before day 28)
Secondary	Hospital/ICU length of stay		29 days or less (may be discharged before day 28)
Secondary	ICU admission		29 days or less (may be discharged from critical care before day 28)