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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04330300
Recruitment Status : Suspended (Challenges with funding and very low incidence of COVID-19 at Irish study site)
First Posted : April 1, 2020
Last Update Posted : June 30, 2020
Sponsor:
Information provided by (Responsible Party):
Prof. John William McEvoy, National University of Ireland, Galway, Ireland

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

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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


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




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



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04330300


Locations
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Ireland
University Hospital Galway
Galway, Ireland, H91 YR71
Sponsors and Collaborators
National University of Ireland, Galway, Ireland
Investigators
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Principal Investigator: John William McEvoy, MBBCh MHS National University of Ireland, Galway, Ireland
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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    Key Record Dates
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

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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:
COVID-19
Calcium Channel Blockers
Hypertension
Blood Pressure
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
Diuretics
ACE-2
Additional relevant MeSH terms:
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Calcium Channel Blockers
Coronavirus Infections
Hypertension
Vascular Diseases
Cardiovascular Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Losartan
Verapamil
Felodipine
Amlodipine
Valsartan
Hydrochlorothiazide
Telmisartan
Candesartan
Ramipril
Olmesartan
Enalapril
Lisinopril
Irbesartan
Chlorthalidone
Diltiazem
Perindopril
Benazepril
Captopril
Nicardipine
Nimodipine
Indapamide