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

June 26, 2020 updated by: Prof. John William McEvoy, National University of Ireland, Galway, Ireland

The CORONAvirus Disease 2019 Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker InvestigatiON (CORONACION) Randomized Clinical Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2414

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ireland
      • Galway, Ireland, H91 YR71
        • University Hospital Galway

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

56 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • Hydrochlorothiazide, metolazone, chlorthalidone, chlorothiazide, bendroflumethiazide, indapamide
Drug: Calcium Channel Blockers
Anti-hypertensive (Active Arm)
Other Names:
  • 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 Names:
  • Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril
Drug: Angiotensin receptor blocker
Anti-hypertensive (Control Arm)
Other Names:
  • Candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Covid-19 positive participants who die
Time Frame: 12 months
Time from randomization to the first occurrence of above
12 months
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
12 months
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
12 months
Number of SARS-CoV-2 positive participants
Time Frame: 12 months
Time from randomization to the first occurrence of above
12 months
Maximum troponin T value (ng/L) among Covid-19 positive participants who require acute hospitalization
Time Frame: 12 months
12 months
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)
12 months
All-cause mortality
Time Frame: 12 months
Time from randomization to the first occurrence of above
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National University of Ireland, Galway, Ireland

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: John William McEvoy, MBBCh MHS, National University of Ireland, Galway, Ireland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 30, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 1, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 30, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 26, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • C.A. 2348

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Sharing Time Frame

12-24 months

IPD Sharing Access Criteria

To be determined

IPD Sharing Supporting Information Type

  • Study Protocol
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings