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

• ClinicalTrials.gov Identifier: NCT04330300
• Recruitment Status: Suspended
• First Posted: April 1, 2020
• Last Update Posted: June 30, 2020
• Sponsor: National University of Ireland, Galway, Ireland
• Information provided by (Responsible Party): Prof. John William McEvoy, National University of Ireland, Galway, Ireland

Tracking Information

• First Submitted Date: March 30, 2020
• First Posted Date: April 1, 2020
• Last Update Posted Date: June 30, 2020
• Actual Study Start Date: April 30, 2020
• Estimated Primary Completion Date: July 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 9, 2020)

• Number of Covid-19 positive participants who die [ Time Frame: 12 months ]
  Time from randomization to the first occurrence of above
• 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
• 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
• Number of SARS-CoV-2 positive participants [ Time Frame: 12 months ]
  Time from randomization to the first occurrence of above
• 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 ]
  Performed in a random sub-sample of the cohort (both study arms)
• All-cause mortality [ Time Frame: 12 months ]
  Time from randomization to the first occurrence of above

Original Secondary Outcome Measures (submitted: March 30, 2020)

• Number of Covid-19 positive participants who die [ Time Frame: 12 months ]
  Time from randomization to the first occurrence of above
• 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
• 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
• Number of SARS-CoV-2 positive participants [ Time Frame: 12 months ]
  Time from randomization to the first occurrence of above
• 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 ]
  Performed in a random sub-sample of the cohort (both study arms)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Coronavirus (COVID-19) ACEi/ARB Investigation
• Official Title: The CORONAvirus Disease 2019 Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker InvestigatiON (CORONACION) Randomized Clinical Trial
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Hypertension
• COVID-19

Intervention

• 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
• 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

Study Arms

• 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.
  Interventions:

  • Drug: Thiazide or Thiazide-like diuretics
  • Drug: Calcium Channel Blockers
• 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.
  Interventions:

  • Drug: ACE inhibitor
  • Drug: Angiotensin receptor blocker

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: March 30, 2020): 2414
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2021
• Estimated Primary Completion Date: July 31, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Ireland

Administrative Information

• NCT Number: NCT04330300
• Other Study ID Numbers: C.A. 2348
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: 12-24 months
• Access Criteria: To be determined

• Current Responsible Party: Prof. John William McEvoy, National University of Ireland, Galway, Ireland
• Original Responsible Party: Same as current
• Current Study Sponsor: National University of Ireland, Galway, Ireland
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: John William McEvoy, MBBCh MHS; National University of Ireland, Galway, Ireland

• PRS Account: National University of Ireland, Galway, Ireland
• Verification Date: June 2020