Coronavirus (COVID-19) ACEi/ARB Investigation (CORONACION)

• ClinicalTrials.gov Identifier: NCT04330300
• Recruitment Status: Suspended
• First Posted: April 1, 2020
• Last Update Posted: June 30, 2020
• Sponsor: National University of Ireland, Galway, Ireland
• Information provided by (Responsible Party): Prof. John William McEvoy, National University of Ireland, Galway, Ireland

Study Description

Brief Summary:

Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is known to require the angiotensin-converting enzyme 2 (ACE-2) receptor for uptake into the human body, there have been questions about whether medications that upregulate ACE-2 receptors might increase the risk of infection and subsequent complications. One such group of medications are anti-hypertensives that block the renin-angiotensin system, including both angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB). Both ACEi and ARB are widely used for the treatment of hypertension. Early reports from China and Italy suggest that many of those who die from COVID-19 have a coexisting history of hypertension. Consequently, there have been questions raised as to whether these 2 types of blood pressure medication might increase the risk of death among patients with COVID-19. However, it is well known that the prevalence of hypertension increases linearly with age. Therefore, it is possible that the high prevalence of hypertension and ACEi/ARB use among persons who die from COVID-19 is simply confounded by age (older people are at risk of both a history of hypertension and dying from COVID-19). Whether these commonly prescribed blood pressure medications increase the risk of COVID-19 or not remains unanswered. Statements from professional cardiology societies on both sides of the Atlantic have called for urgent research into this question. Our study aims to randomize patients with primary (essential) hypertension who are already taking ACEi/ARB to either switch to an alternative BP medication or continue with the ACEi/ARB that they have already been prescribed. Adults with compelling indications for ACEi/ARB will not be enrolled.

Condition or disease	Intervention/treatment	Phase
Hypertension; COVID-19	Drug: Thiazide or Thiazide-like diuretics; Drug: Calcium Channel Blockers; Drug: ACE inhibitor; Drug: Angiotensin receptor blocker	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 2414 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: The CORONAvirus Disease 2019 Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker InvestigatiON (CORONACION) Randomized Clinical Trial
• Actual Study Start Date: April 30, 2020
• Estimated Primary Completion Date: July 31, 2021
• Estimated Study Completion Date: December 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Alternative anti-hypertensive medication; Switch to an alternative BP medication (specifically a Calcium channel blocker [CCB] or Thiazide/Thiazide-like diuretic at an equipotent blood pressure lowering dose). The choice of either CCB or Thiazide/Thiazide-like anti-hypertensive provided as alternative therapy will be at the discretion of the patient's treating physician.	Drug: Thiazide or Thiazide-like diuretics; Anti-hypertensive (Active Arm); Other Name: Hydrochlorothiazide, metolazone, chlorthalidone, chlorothiazide, bendroflumethiazide, indapamide; Drug: Calcium Channel Blockers; Anti-hypertensive (Active Arm); Other Name: Amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nimodipine, nitrendipine, verapamil
Active Comparator: Continue ACEi/ARB antihypertensive; Continue with either the ACEi (Angiotensin Converting Enzyme Inhibitor) or the Angiotensin Receptor Blocker (ARB) that had already been prescribed for the treatment of hypertension.	Drug: ACE inhibitor; Anti-hypertensive (Control Arm); Other Name: Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril; Drug: Angiotensin receptor blocker; Anti-hypertensive (Control Arm); Other Name: Candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan

Outcome Measures

Primary Outcome Measures :

1. Number of Covid-19 positive participants who die, require intubation in ICU, or require hospitalization for non-invasive ventilation (NIV) [ Time Frame: 12 months ]
   Time from randomization to the first occurrence of any of the clinical events above

Secondary Outcome Measures :

1. Number of Covid-19 positive participants who die [ Time Frame: 12 months ]
   Time from randomization to the first occurrence of above
2. Number of Covid-19 positive participants who require intubation in intensive care unit (ICU) [ Time Frame: 12 months ]
   Time from randomization to the first occurrence of above
3. Number of Covid-19 positive participants who require hospitalization for non-invasive ventilation (NIV) [ Time Frame: 12 months ]
   Time from randomization to the first occurrence of above
4. Number of SARS-CoV-2 positive participants [ Time Frame: 12 months ]
   Time from randomization to the first occurrence of above
5. Maximum troponin T value (ng/L) among Covid-19 positive participants who require acute hospitalization [ Time Frame: 12 months ]
6. 24 hour mean systolic BP (mmHg) on ambulatory BP monitoring [ Time Frame: 12 months ]
   Performed in a random sub-sample of the cohort (both study arms)
7. All-cause mortality [ Time Frame: 12 months ]
   Time from randomization to the first occurrence of above

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men and non-pregnant women aged 60 or over
• Known diagnosis of hypertension
• Current use of ACEi or ARB for the treatment of hypertension
• COVID-19 naïve (i.e. not known to be infected)
• English speaker

Exclusion Criteria:

• Known diabetic nephropathy
• Known heart failure with reduced ejection fraction
• Resistant hypertension (defined as blood pressure that remains above goal despite concurrent use of three anti-hypertensive agents of different classes, one of which should be a diuretic, or as blood pressure that is controlled with four or more medications)
• Contraindications or allergies to CCB or Thiazide
• Unconscious patients
• Current psychiatric in-patients
• Patients in an emergency medical setting
• Inability to consent

Contacts and Locations

Locations

Ireland

University Hospital Galway

Galway, Ireland, H91 YR71

Sponsors and Collaborators

National University of Ireland, Galway, Ireland

Investigators

• Principal Investigator: John William McEvoy, MBBCh MHS; National University of Ireland, Galway, Ireland

More Information

• Responsible Party: Prof. John William McEvoy, Professor of Preventive Cardiology, National University of Ireland, Galway, Ireland
• ClinicalTrials.gov Identifier: NCT04330300
• Other Study ID Numbers: C.A. 2348
• First Posted: April 1, 2020
• Last Update Posted: June 30, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: 12-24 months
• Access Criteria: To be determined

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Prof. John William McEvoy, National University of Ireland, Galway, Ireland:

Hypertension; Blood Pressure; COVID-19; Coronavirus Disease 2019; Novel Coronavirus; Coronavirus; Cardiovascular Diseases; Pandemic; Critical Care; Intubation; Noninvasive Ventilation; Angiotensin Converting Enzyme; Angiotensin Converting Enzyme 2; Renin-Angiotensin System; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Calcium Channel Blockers; Diuretics; ACE-2

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Hypertension; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases; Losartan; Verapamil; Felodipine; Amlodipine; Valsartan; Hydrochlorothiazide; Telmisartan; Candesartan; Ramipril; Olmesartan; Enalapril; Lisinopril; Irbesartan; Chlorthalidone; Perindopril