A Phase 3 interventional study of Losartan and Valsartan in Covid19 and SARS-CoV Infection, sponsored by University of British Columbia. Terminated at 13 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-16.
Sponsored by University of British Columbia · Phase 3, Interventional, and Treatment
SARS-CoV-2 is a member of a class of viruses: angiotensin converting enzyme 2 (ACE2)-binding viruses that study calls "ABVs". The World Health Organization (WHO) and others are performing randomized controlled trials (RCTs) of vaccines and novel antivirals to address SARS-CoV-2 directly. However, the critical illness complications of COVID-19 are caused in part by SARS-CoV-2's binding and inhibiting ACE2 and the consequent host response.
ACE 2 is the receptor for H1N1, H5N1, and SARS-CoV-2. After binding ACE2, SARS-CoV-2 is endocytosed, and surface ACE2 is down-regulated, increasing angiotensin II (ATII a potent vasoconstrictor) in COVID-19. The original ARBs limits lung injury in murine influenza H7N9 and decreases viral titre and RNA.
Study has a unique opportunity to complement vaccine and anti-viral RCTs with an RCT modulating the host response using an angiotensin II type 1 receptor blocker (ARBs) to decrease the mortality of hospitalized COVID-19 patient.
PURPOSE: There is clinical equipoise around the safety and efficacy of ARBs in COVID-19, but there are few RCTs of ARBs in COVID-19. Guo and colleagues' meta-analysis showed that ARBs/ACE inhibitor use was associated with decreased mortality. Our structured literature review (Cheng et al., submitted) shows that SARS-CoV-2 and other viruses that bind ACE2 cause acute cardiac injury in nearly 50% of cases. Safety concerns of ARBs in COVID-19 arise because ARBs increase cardiac ACE2, potentially increasing SARS-CoV-2 cellular uptake and worsening outcomes. On the other hand, ARBs block the effects of excess angiotensin II and could be beneficial. Our proposed ARBs CORONA II Phase 3 RCT will establish whether ARBs can decrease mortality in hospitalized COVID-19 patients.
HYPOTHESIS:
Primary - ARBs (losartan, valsartan, azilsartan, candesartan, eprosartan, irbesartan, olmesartan, telmisartan) decreases mortality and are safe in hospitalized COVID-19 infected adults compared to standard of care.
Secondary - ACE pathway proteins (ATI, AT1-7, ATII, ACE and ACE2 levels), cytokines and metabolomics/proteomics predict mortality and efficacy of ARBs in hospitalized COVID19 adults.
RESEARCH DESIGN: Study will assess ARBs (losartan, valsartan, azilsartan, candesartan, eprosartan, irbesartan, olmesartan, telmisartan) (see 6.3 Intervention for more) vs. usual care for safety and efficacy in decreasing organ dysfunction and mortality of hospitalized adults with COVID-19. Dr. Srinivas Murthy and Dr Rob Fowler, co-investigators herein and PIs of the CATCO RCT in Canada, Dr. John Marshall, co-investigator herein and PI of REMAPCAP, and Dr. Russell have coordinated alignment by allowing co-enrollment and harmonization of data and sample collection and primary endpoints.
6,687 studies on the registry are indexed under Infections; 807 are open to participants now.
This study's enrollment of 341 is above the median of 120 across 4,200 interventional studies indexed under Infections.
Browse Infections studies →University of British Columbia is the lead sponsor of 1,309 studies on the registry; 253 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 1 (17%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Patients will initially receive initial dose of oral ARBs, increased to higher dose after 24 hours and then increased to a max dose after another 24 hours, dependent on tolerance. Patient will remain at dose for duration of hospital (max of 3 months if still hospitalized). Tolerance is defined as having no severe adverse events 24 hours after the first dose. Investigators and/or attending physicians discretion may dictate that dose will not be increased, at which point dose will stay at initial or higher dose.
Drug: Losartan · Drug: Valsartan · Drug: Azilsartan · Drug: Candesartan · Drug: Eprosartan · Drug: Irbesartan · Drug: Olmesartan · Drug: Telmisartan
Usual care for duration of hospitalization for up to 3 months if still hospitalized. Due to the lack of clinical guidance from this emergent disease, this may vary dependent on Institution and/or country
Oral losartan 25 mg, stepped up to 50 mg and then up to 100 mg peak dose, as tolerated.
Also known as: Cozaar
Oral Valsartan 40 mg, stepped up to 80 mg and then up to 160 mg peak dose, as tolerated.
Also known as: Diovan
Oral Azilsartan 40 mg, and stepped up to 80 mg.
Also known as: Edarbi
Oral Candesartan 8 mg, stepped up to 16 mg and then up to 32 mg peak dose, as tolerated.
Also known as: Atacand
Oral Eprosartan 400 mg, stepped up to 600 mg and then up to 800 mg peak dose, as tolerated.
Also known as: Teventen
Oral Irbesartan 75 mg, stepped up to 150 mg and then up to 300 mg peak dose, as tolerated.
Also known as: Avapro
Oral Olmesartan 10 mg, stepped up to 20 mg and then up to 40 mg peak dose, as tolerated.
Also known as: Olmetec
Oral Azilsartan 40 mg, and stepped up to 80 mg.
Also known as: Micardis
Mortality
Survival status
Time frame: 28 days
Hospital Mortality
Survival status
Time frame: up to 6 months
ICU Admission
Location within hospital (ICU or wards)
Time frame: up to 6 months
Days alive and free of vasopressors, ventilation, and renal replacement therapy
Survival and ICU support status
Time frame: up to 14 days
SOFA score
Sequential Organ Failure Assessment (SOFA) score
Time frame: 28 days
Acute cardiac injury
Use of inotropic agents and increase(s) of of troponin and/or NT-proBNP from admission level
Time frame: 6 months
Severe adverse events
Severe adverse effects of ARBs and mortality
Time frame: 6 months
Mortality
Survival status
Time frame: at 1, 3 and 6 months
Plan to share: No
No publications or documents are linked to this record.
This study is terminated, as verified in Feb 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of British Columbia