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

National University of Ireland, Galway, Ireland

Status and phase: Suspended; Phase 4

Conditions: COVID-19; Hypertension

Treatments: Drug: ACE inhibitor; Drug: Angiotensin receptor blocker; Drug: Calcium Channel Blockers; Drug: Thiazide or Thiazide-like diuretics

Study type: Interventional

Funder types: Other

Identifiers

NCT04330300

C.A. 2348

Details and patient eligibility

About

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.

Enrollment: 2,414 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,414 participants in 2 patient groups

Alternative anti-hypertensive medication

Experimental group

Description:

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.

Treatment:

Drug: Thiazide or Thiazide-like diuretics

Drug: Calcium Channel Blockers

Continue ACEi/ARB antihypertensive

Active Comparator group

Description:

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.

Treatment:

Drug: Angiotensin receptor blocker

Drug: ACE inhibitor