Coronavirus (COVID-19) ACEi/ARB Investigation

NCT04330300 | Suspended Phase 4 DMC

• 1 other identifier: C.A. 2348
• Study Type: interventional
• Target: 2,414
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

  12 months

Secondary Outcomes (7)

• Number of Covid-19 positive participants who die

  12 months

• Number of Covid-19 positive participants who require intubation in intensive care unit (ICU)

  12 months

• Number of Covid-19 positive participants who require hospitalization for non-invasive ventilation (NIV)

  12 months

• Number of SARS-CoV-2 positive participants

  12 months

• Maximum troponin T value (ng/L) among Covid-19 positive participants who require acute hospitalization

  12 months

Study Arms (2)

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.

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.

Drug: ACE inhibitor; Drug: Angiotensin receptor blocker

Interventions

Thiazide or Thiazide-like diuretics DRUG

Anti-hypertensive (Active Arm)

Also known as: Hydrochlorothiazide, metolazone, chlorthalidone, chlorothiazide, bendroflumethiazide, indapamide

Alternative anti-hypertensive medication

Calcium Channel Blockers DRUG

Anti-hypertensive (Active Arm)

Also known as: Amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nimodipine, nitrendipine, verapamil

Alternative anti-hypertensive medication

ACE inhibitor DRUG

Anti-hypertensive (Control Arm)

Also known as: Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril

Continue ACEi/ARB antihypertensive

Angiotensin receptor blocker DRUG

Anti-hypertensive (Control Arm)

Also known as: Candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan

Continue ACEi/ARB antihypertensive

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National University of Ireland, Galway, Ireland: lead

Study Sites (1)

University Hospital Galway

Galway, H91 YR71, Ireland

Location

MeSH Terms

Conditions

Hypertension; COVID-19; Coronavirus Infections; Cardiovascular Diseases

Interventions

Thiazides; Hydrochlorothiazide; Metolazone; Chlorthalidone; Chlorothiazide; Bendroflumethiazide; Indapamide; Calcium Channel Blockers; Amlodipine; Diltiazem; Felodipine; Nicardipine; Nifedipine; Nimodipine; Nitrendipine; Verapamil; Angiotensin-Converting Enzyme Inhibitors; benazepril; Captopril; Enalapril; Fosinopril; Lisinopril; Perindopril; Quinapril; Ramipril; trandolapril; Angiotensin Receptor Antagonists; candesartan; eprosartan; Irbesartan; Losartan; olmesartan; Telmisartan; Valsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfur Compounds; Organic Chemicals; Benzothiadiazines; Sulfonamides; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amides; Quinazolinones; Quinazolines; Benzenesulfonamides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Isoindoles; Indoles; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Cardiovascular Agents; Therapeutic Uses; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Benzazepines; Nicotinic Acids; Phenethylamines; Ethylamines; Amines; Protease Inhibitors; Enzyme Inhibitors; Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Dipeptides; Oligopeptides; Peptides; Phosphinic Acids; Organophosphorus Compounds; Tetrahydroisoquinolines; Isoquinolines; Biphenyl Compounds; Spiro Compounds; Tetrazoles; Azoles; Polycyclic Compounds; Imidazoles; Benzimidazoles; Valine; Amino Acids, Branched-Chain; Amino Acids, Essential

Study Officials

• John William McEvoy, MBBCh MHS

  National University of Ireland, Galway, Ireland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Preventive Cardiology

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 1, 2020
• Study Start: April 30, 2020
• Primary Completion: July 31, 2021
• Study Completion: December 1, 2021
• Last Updated: June 30, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: 12-24 months
• Access Criteria: To be determined

Locations

IE (1)