Clinical trial NCT04330300: Coronavirus (COVID-19) ACEi/ARB Investigation
Official title: The CORONAvirus Disease 2019 Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker InvestigatiON (CORONACION) Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE4
Conditions: Hypertension
COVID-19
Keywords: 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
Lead sponsor: National University of Ireland, Galway, Ireland
Sponsor class: OTHER
First posted: 2020-04-01
Enrollment: 2414
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: Number of Covid-19 positive participants who die, require intubation in ICU, or require hospitalization for non-invasive ventilation (NIV)
timeFrame: 12 months
Secondary outcomes:
measure: Number of Covid-19 positive participants who die
timeFrame: 12 months
measure: Number of Covid-19 positive participants who require intubation in intensive care unit (ICU)
timeFrame: 12 months
measure: Number of Covid-19 positive participants who require hospitalization for non-invasive ventilation (NIV)
timeFrame: 12 months
measure: Number of SARS-CoV-2 positive participants
timeFrame: 12 months
measure: Maximum troponin T value (ng/L) among Covid-19 positive participants who require acute hospitalization
timeFrame: 12 months
measure: 24 hour mean systolic BP (mmHg) on ambulatory BP monitoring
timeFrame: 12 months
measure: All-cause mortality
timeFrame: 12 months
Other outcomes:
Locations:
city: Galway
country: Ireland
facility: University Hospital Galway
Study officials:
affiliation: National University of Ireland, Galway, Ireland
name: John William McEvoy, MBBCh MHS
role: PRINCIPAL_INVESTIGATOR
References: