HypertensionPhase 4CORONACIONNCT04330300
Coronavirus (COVID-19) ACEi/ARB Investigation
A Phase 4 study testing Thiazide or Thiazide-like diuretics, Calcium Channel Blockers and ACE inhibitor in people with Hypertension and COVID-19, run by National University of Ireland, Galway, Ireland at 1 site in Ireland.
Trial 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… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Hypertension, COVID-19
- What is being tested?
- Thiazide or Thiazide-like diuretics, Calcium Channel Blockers and ACE inhibitor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,414 participants
- Where
- 1 siteIreland
- Study dates
- 30 Apr 2020to 1 Dec 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Hypertension, COVID-19
- Being tested
- Thiazide or Thiazide-like diuretics, Calcium Channel Blockers, ACE inhibitor, Angiotensin receptor blocker
- 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
- Medical subject headings
- Hypertension, COVID-19, Coronavirus Infections, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thiazide or Thiazide-like diureticsDrug
Also called Hydrochlorothiazide, metolazone, chlorthalidone, chlorothiazide, bendroflumethiazide, indapamide
Anti-hypertensive (Active Arm)
Calcium Channel BlockersDrug
Also called Amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nimodipine, nitrendipine, verapamil
Anti-hypertensive (Active Arm)
ACE inhibitorDrug
Also called Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril
Anti-hypertensive (Control Arm)
Angiotensin receptor blockerDrug
Also called Candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan
Anti-hypertensive (Control Arm)
| Study group | Role | What they receive |
|---|---|---|
| Alternative anti-hypertensive medication | Experimental | 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. Receives: Drug: Thiazide or Thiazide-like diuretics; Drug: Calcium Channel Blockers |
| Continue ACEi/ARB antihypertensive | Active comparator | 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. Receives: Drug: ACE inhibitor; Drug: Angiotensin receptor blocker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Covid-19 positive participants who die, require intubation in ICU, or require hospitalization for non-invasive ventilation (NIV)
Time from randomization to the first occurrence of any of the clinical events above
Measured: 12 months
Secondary outcomes (7)
Number of Covid-19 positive participants who die
Time from randomization to the first occurrence of above
Measured: 12 months
Number of Covid-19 positive participants who require intubation in intensive care unit (ICU)
Time from randomization to the first occurrence of above
Measured: 12 months
Number of Covid-19 positive participants who require hospitalization for non-invasive ventilation (NIV)
Time from randomization to the first occurrence of above
Measured: 12 months
Number of SARS-CoV-2 positive participants
Time from randomization to the first occurrence of above
Measured: 12 months
Maximum troponin T value (ng/L) among Covid-19 positive participants who require acute hospitalization
Measured: 12 months
24 hour mean systolic BP (mmHg) on ambulatory BP monitoring
Performed in a random sub-sample of the cohort (both study arms)
Measured: 12 months
All-cause mortality
Time from randomization to the first occurrence of above
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start30 Apr 2020
- Primary completion31 Jul 2021 (estimated)
- Study completion1 Dec 2021 (estimated)
Why it stopped: Challenges with funding and very low incidence of COVID-19 at Irish study site
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,414 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University of Ireland, Galway, Ireland
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. John William McEvoy, National University of Ireland, Galway, Ireland
- Investigators
- John William McEvoy, MBBCh MHS, Principal investigator, National University of Ireland, Galway, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04330300
- Sponsor's protocol ID
- C.A. 2348
- Acronym
- CORONACION
- Status last verified
- Jun 2020
- First submitted
- 30 Mar 2020
- Last updated
- 30 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The CORONAvirus Disease 2019 Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker InvestigatiON (CORONACION) Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04330300
- Acronym / sponsor ID
- CORONACION / C.A. 2348
- Conditions
- Hypertension, COVID-19
- Keywords
- Hypertension, Blood Pressure, COVID-19, Coronavirus Disease 2019, Novel Coronavirus, Coronavirus, Cardiovascular Diseases, Pandemic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Challenges with funding and very low incidence of COVID-19 at Irish study site
- Enrolment
- 2,414 participants (estimated)
- Lead sponsor
- National University of Ireland, Galway, IrelandUniversity, hospital or other
- Study start
- 30 Apr 2020 (actual)
- Primary completion
- 31 Jul 2021 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 1 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alternative anti-hypertensive medication | Experimental | Drug: Thiazide or Thiazide-like diuretics, Drug: Calcium Channel BlockersSwitch 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. |
| Continue ACEi/ARB antihypertensive | Active comparator | Drug: ACE inhibitor, Drug: Angiotensin receptor blockerContinue with either the ACEi (Angiotensin Converting Enzyme Inhibitor) or the Angiotensin Receptor Blocker (ARB) that had already been prescribed for the treatment of hypertension. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thiazide or Thiazide-like diureticsAlso: Hydrochlorothiazide, metolazone, chlorthalidone, chlorothiazide, bendroflumethiazide, indapamideAnti-hypertensive (Active Arm) | Drug | Alternative anti-hypertensive medication |
| Calcium Channel BlockersAlso: Amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nimodipine, nitrendipine, verapamilAnti-hypertensive (Active Arm) | Drug | Alternative anti-hypertensive medication |
| ACE inhibitorAlso: Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolaprilAnti-hypertensive (Control Arm) | Drug | Continue ACEi/ARB antihypertensive |
| Angiotensin receptor blockerAlso: Candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartanAnti-hypertensive (Control Arm) | Drug | Continue ACEi/ARB antihypertensive |
Primary outcome
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
7 secondary outcomes
Number of Covid-19 positive participants who die
Time frame: 12 months
Number of Covid-19 positive participants who require intubation in intensive care unit (ICU)
Time frame: 12 months
Number of Covid-19 positive participants who require hospitalization for non-invasive ventilation (NIV)
Time frame: 12 months
Number of SARS-CoV-2 positive participants
Time frame: 12 months
Maximum troponin T value (ng/L) among Covid-19 positive participants who require acute hospitalization
Time frame: 12 months
24 hour mean systolic BP (mmHg) on ambulatory BP monitoring
Time frame: 12 months
All-cause mortality
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2020.
- Individual participant dataSharing planned: Yes
Related trials for Hypertension
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John William McEvoy, MBBCh MHS principal investigator
National University of Ireland, Galway, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Thiazide or Thiazide-like diuretics, Calcium Channel Blockers and ACE inhibitor in people with Hypertension and COVID-19, run by National University of Ireland, Galway, Ireland at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 30 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Covid-19 positive participants who die, require intubation in ICU, or require hospitalization for non-invasive ventilation (NIV) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2020.