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Trial record 3 of 11 for:    utah and outpatient | COVID-19

ACEI or ARB and COVID-19 Severity and Mortality in US Veterans

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: NCT04467931
Recruitment Status : Active, not recruiting
First Posted : July 13, 2020
Last Update Posted : November 3, 2020
Sponsor:
Collaborators:
VA Salt Lake City Health Care System
University of Pennsylvania
Wake Forest University Health Sciences
University of Florida
Johns Hopkins Bloomberg School of Public Health
Boston University
Northwestern University
Edith Nourse Rogers Memorial Veterans Hospital
Columbia University
MedStar Georgetown University Hospital
Information provided by (Responsible Party):
Adam Bress, University of Utah

Brief Summary:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, enters type II pneumocytes using angiotensin-converting enzyme 2 (ACE2). It is unclear whether ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) increase, decrease, or have no significant effect on ACE2 expression or activity. Therefore, ACEI and ARB may be harmful, beneficial, or have no impact on Coronavirus Disease 2019 severity and mortality. The Specific Aims of this observational study are: (1) Among SARS-CoV-2-positive outpatients, compare all-cause hospitalization and mortality rates between: 1.1 Current users of a range of doses of ACEI/ARB- vs. non- ACEI/ARB-based regimens, and 1.2 Current users of a range of doses of ACEI- vs. ARB-based regimens, and (2) Among those hospitalized for COVID-19, compare all-cause mortality between: 2.1 Current users of a range of doses of ACEI/ARB- vs. non- ACEI/ARB-based regimens, and 2.2 Current users of a range of doses of ACEI- vs. ARB-based regimens.

Condition or disease Intervention/treatment
Hypertension COVID Drug: ACEI/ARB Drug: Non-ACEI/ARB Drug: ACEI Drug: ARB

Detailed Description:
The Coronavirus Disease 2019 (COVID-19) pandemic has killed >129,000 Americans as of June 30, 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, enters type II pneumocytes using angiotensin-converting enzyme 2 (ACE2). ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase ACE2 expression. Theoretically, if ACEI/ARB use increases ACE2 expression in the lungs, ACEI/ARBs could promote SARS-CoV-2 entry into type II pneumocytes and worsen COVID-19 infection. In contrast, other evidence suggests that ACEI/ARBs may mitigate virus-induced inflammatory responses in the lungs by upregulating ACE2-mediated generation of the vasodilator and anti-inflammatory protein angiotensin-(1-7), thereby preventing tissue damage. Few data exist on the direction or magnitude of the association between ACEI/ARB use and COVID-19 severity, and whether these associations differ between ACEIs and ARBs. Because ACEI/ARBs are among the most commonly used prescription medications, it is critical to determine if ACEI/ARB users have a differential risk of more severe COVID-19 infection compared to non-users. The objective of this study is to reduce morbidity and mortality of the COVID-19 pandemic by generating timely evidence on the direction and magnitude of the association between ACEI/ARB use and COVID-19 severity and mortality.

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Study Type : Observational
Estimated Enrollment : 10000 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Association Between Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use and COVID-19 Severity and Mortality Among US Veterans
Actual Study Start Date : January 19, 2020
Actual Primary Completion Date : October 21, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
1.1 Outpatient SARS-CoV-2 Positive, ACEI/ARB vs non-ACEI/ARB
Among Veterans with treated hypertension and without compelling indications who test positive for SARS-CoV-2, compare all-cause hospitalization and all-cause mortality rates between current users of a range of doses of ACEI/ARB- vs. non-ACEI/ARB-based regimens.
Drug: ACEI/ARB
Veterans will be categorized as exposed to ACEI/ARB if they have one or more pharmacy fills for an oral ACEI or an ARB in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.
Other Names:
  • benazepril
  • captopril
  • enalapril
  • fosinopril
  • lisinopril
  • moexipril
  • perindopril
  • quinapril
  • ramipril
  • trandolapril
  • azilsartan
  • candesartan
  • eprosartan
  • irbesartan
  • losartan
  • olmesartan
  • telmisartan
  • valsartan

Drug: Non-ACEI/ARB
Veterans will be categorized as exposed to a non-ACEI/ARB if they have one or more pharmacy fills for an oral non-ACEI or ARB medication in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an ACEI/ARB medication in the 90 days (± 14 days) prior to each Veteran's index date. Specific drug classes include: aldosterone receptor antagonist, beta-blocker, calcium channel blocker, centrally-acting drug, direct arterial vasodilator, direct renin inhibitor, thiazide diuretic, loop diuretic, and potassium sparing diuretic.
Other Names:
  • doxazosin
  • prazosin
  • terazosin
  • acebutolol
  • nebivolol
  • atenolol
  • betaxolol
  • bisoprolol
  • metoprolol
  • pindolol
  • penbutolol
  • carvedilol
  • labetalol
  • nadolol
  • propranolol
  • timolol
  • amlodipine
  • felodipine
  • isradipine
  • nifedipine
  • nicardipine
  • nisoldipine
  • diltiazem
  • verapamil
  • clonidine
  • guanfacine
  • guanabenz
  • methyldopa
  • reserpine
  • hydralazine
  • minoxidil
  • aliskiren
  • spironolactone
  • eplerenone
  • bumetanide
  • furosemide
  • ethacrynic acid
  • torsemide
  • amiloride
  • triamterene
  • bendroflumethiazide
  • chlorothiazide
  • chlorthalidone
  • hydrochlorothiazide
  • indapamide
  • metolazone

1.2 Outpatient SARS-CoV-2 Positive, ACEI vs. ARB
Among Veterans with treated hypertension who test positive for SARS-CoV-2, compare all-cause hospitalization and all-cause mortality rates between current users of a range of doses of ACEI- vs. ARB-based regimens.
Drug: ACEI
Veterans will be categorized as exposed to an ACEI if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ARB in the 90 days (± 14 days) prior to each Veteran's index date.
Other Names:
  • benazepril
  • captopril
  • enalapril
  • fosinopril
  • lisinopril
  • moexipril
  • perindopril
  • quinapril
  • ramipril
  • trandolapril

Drug: ARB
Veterans will be categorized as exposed to an ARB if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.
Other Names:
  • azilsartan
  • candesartan
  • eprosartan
  • irbesartan
  • losartan
  • olmesartan
  • telmisartan
  • valsartan

2.1 COVID-19 Hospitalized, ACEI/ARB vs non-ACEI/ARB
Among Veterans with treated hypertension and without compelling indications who are hospitalized for COVID-19, compare all-cause mortality rates between current users of a range of doses of ACEI/ARB- vs. non-ACEI/ARB-based regimens.
Drug: ACEI/ARB
Veterans will be categorized as exposed to ACEI/ARB if they have one or more pharmacy fills for an oral ACEI or an ARB in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.
Other Names:
  • benazepril
  • captopril
  • enalapril
  • fosinopril
  • lisinopril
  • moexipril
  • perindopril
  • quinapril
  • ramipril
  • trandolapril
  • azilsartan
  • candesartan
  • eprosartan
  • irbesartan
  • losartan
  • olmesartan
  • telmisartan
  • valsartan

Drug: Non-ACEI/ARB
Veterans will be categorized as exposed to a non-ACEI/ARB if they have one or more pharmacy fills for an oral non-ACEI or ARB medication in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an ACEI/ARB medication in the 90 days (± 14 days) prior to each Veteran's index date. Specific drug classes include: aldosterone receptor antagonist, beta-blocker, calcium channel blocker, centrally-acting drug, direct arterial vasodilator, direct renin inhibitor, thiazide diuretic, loop diuretic, and potassium sparing diuretic.
Other Names:
  • doxazosin
  • prazosin
  • terazosin
  • acebutolol
  • nebivolol
  • atenolol
  • betaxolol
  • bisoprolol
  • metoprolol
  • pindolol
  • penbutolol
  • carvedilol
  • labetalol
  • nadolol
  • propranolol
  • timolol
  • amlodipine
  • felodipine
  • isradipine
  • nifedipine
  • nicardipine
  • nisoldipine
  • diltiazem
  • verapamil
  • clonidine
  • guanfacine
  • guanabenz
  • methyldopa
  • reserpine
  • hydralazine
  • minoxidil
  • aliskiren
  • spironolactone
  • eplerenone
  • bumetanide
  • furosemide
  • ethacrynic acid
  • torsemide
  • amiloride
  • triamterene
  • bendroflumethiazide
  • chlorothiazide
  • chlorthalidone
  • hydrochlorothiazide
  • indapamide
  • metolazone

2.2 COVID-19 Hospitalized, ACEI vs. ARB
Among Veterans with treated hypertension who are hospitalized for COVID-19, compare all-cause mortality rates between current users of a range of doses of ACEI- vs. ARB-based regimens.
Drug: ACEI
Veterans will be categorized as exposed to an ACEI if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ARB in the 90 days (± 14 days) prior to each Veteran's index date.
Other Names:
  • benazepril
  • captopril
  • enalapril
  • fosinopril
  • lisinopril
  • moexipril
  • perindopril
  • quinapril
  • ramipril
  • trandolapril

Drug: ARB
Veterans will be categorized as exposed to an ARB if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.
Other Names:
  • azilsartan
  • candesartan
  • eprosartan
  • irbesartan
  • losartan
  • olmesartan
  • telmisartan
  • valsartan




Primary Outcome Measures :
  1. All-Cause-Hospitalization or All-Cause Mortality [ Time Frame: Through study completion (approximately July 31, 2020). ]
    For outpatient Veterans with a positive SARS-CoV-2 test (Aims 1.1 and 1.2), the primary outcome is a composite of time to all-cause hospitalization or all-cause mortality.

  2. All-Cause Mortality [ Time Frame: Through study completion (approximately July 31, 2020). ]
    For Veterans hospitalized with COVID-19 (Aims 2.1 and 2.2), the primary outcome is time to all-cause mortality.


Secondary Outcome Measures :
  1. ICU admission [ Time Frame: Through study completion (approximately July 31, 2020). ]
    For aims 1 and 2, a secondary outcome will be time to intensive care unit (ICU) admission.

  2. Duration of hospitalization [ Time Frame: Through study completion (approximately July 31, 2020). ]
    For aims 1 and 2, a secondary outcome will be duration of hospitalization.

  3. Mechanical ventilation [ Time Frame: Through study completion (approximately July 31, 2020). ]
    For aim 2, a secondary outcome will be time to mechanical ventilation.

  4. Dialysis [ Time Frame: Through study completion (approximately July 31, 2020). ]
    For aim 2, a secondary outcome will be time to in-hospital dialysis.


Other Outcome Measures:
  1. Gastrointestinal bleed [ Time Frame: Through study completion (approximately July 31, 2020). ]
    Time to gastrointestinal bleed. This will be a negative control outcome.

  2. Urinary tract infection [ Time Frame: Through study completion (approximately July 31, 2020). ]
    Time to urinary tract infection. This will be a negative control outcome.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Aim 1: Positive test for SARS-CoV-2 in the outpatient setting, diagnosed with hypertension prior to the index date, and be treated with an antihypertensive in the 90 days prior to the index date.

Aim 2: Hospitalized for COVID-19, diagnosed with hypertension prior to the index date, and be treated with an antihypertensive in the 90 days prior to the index date.

ACEI/ARB vs. non-ACEI/ARB analyses (aims 1.1 and 2.1): Do not have compelling indications that would warrant preferential treatment with an ACEI or an ARB (i.e., diabetes, stroke, chronic kidney disease, heart failure with reduced ejection fraction, or coronary heart disease).

ACEI vs. ARB analyses (aims 1.2 and 2.2): Not concomitantly treated with an ACEI and an ARB in the 90 days prior to the index date, and must be treated with at least an ACEI or an ARB in the 90 days prior to the index date.

Criteria

Inclusion Criteria:

  • Positive SARS-CoV-2 test in the outpatient setting (Aim 1) or hospitalized for COVID-19 (Aim 2)
  • Meet continuous enrollment criteria (≥1 inpatient or any outpatient encounter in each of the two, six-month periods during the 365 days prior to the index date)
  • Do not have data inconsistencies (test patients, not Veterans, multiple death dates in data, or not alive on index date)
  • Diagnosed with hypertension at any point prior to the index date
  • Had at least one prescription dispensed for an antihypertensive medication in the 90 days prior to the index date

Exclusion Criteria:

  • Aim 1.1 and 2.1 (ACEI/ARB vs. non-ACEI/ARB comparison): diagnosed with a compelling indication for ACEI/ARB at any point prior to the index date (i.e., diabetes, stroke, chronic kidney disease, heart failure with reduced ejection fraction, or coronary heart disease)
  • Aim 1.2 and 2.2 (ACE vs. ARB comparison): prescription fills for both an ACEI and an ARB in the 90 days prior to the index date; no prescription fill for an ACEI or an ARB in the 90 days prior to the index date

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): NCT04467931


Locations
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United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
VA Salt Lake City Health Care System
University of Pennsylvania
Wake Forest University Health Sciences
University of Florida
Johns Hopkins Bloomberg School of Public Health
Boston University
Northwestern University
Edith Nourse Rogers Memorial Veterans Hospital
Columbia University
MedStar Georgetown University Hospital
Investigators
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Principal Investigator: Adam P Bress, PharmD, MS University of Utah
  Study Documents (Full-Text)

Documents provided by Adam Bress, University of Utah:
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Responsible Party: Adam Bress, Associate Professor, University of Utah
ClinicalTrials.gov Identifier: NCT04467931    
Other Study ID Numbers: 00132408
First Posted: July 13, 2020    Key Record Dates
Last Update Posted: November 3, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Adam Bress, University of Utah:
angiotensin-converting enzyme inhibitor
angiotensin receptor antagonist
Veterans
antihypertensive medications
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Losartan
Timolol
Propranolol
Metoprolol
Atenolol
Verapamil
Felodipine
Nadolol
Acebutolol
Amlodipine
Valsartan
Hydrochlorothiazide
Telmisartan
Clonidine
Carvedilol
Candesartan
Candesartan cilexetil
Ramipril
Olmesartan
Olmesartan Medoxomil
Enalapril
Enalaprilat
Lisinopril
Irbesartan
Eplerenone
Nebivolol
Chlorthalidone