Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019

Not Applicable

Completed

• Conditions: COVID-19
• Interventions: Other: Discontinuation of ARB/ACEI; Other: Continuation of ARB/ACEI

• Registration Number: NCT04338009
• Lead Sponsor: University of Pennsylvania

Brief Summary

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with a high incidence of acute respiratory distress syndrome (ARDS) and death. Hypertension and cardiovascular disease are risk factors for death in COVID-19. Angiotensin converting enzyme 2 (ACE2), an important component of the renin-angiotensin system, serves as the binding site of SARS-CoV-2 and facilitates host cell entry in the lungs. In experimental models, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to increase ACE2 expression in several organs, potentially promoting viral cell invasion, although these findings are not consistent across studies. Alternatively, ACEIs and ARBs may actually improve mechanisms of host defense or hyperinflammation, ultimately reducing organ injury. Finally, ACEIs and ARBs may have direct renal, pulmonary and cardiac protective benefits in the setting of COVID-19. Therefore, it is unclear if ACEIs and ARBs may be beneficial or harmful in patients with COVID-19. Given the high prevalence of hypertension, cardiovascular and renal disease in the world, the high prevalence of ACEIs or ARBs in these conditions, and the clinical equipoise regarding the continuation vs. discontinuation of ACEIs/ARBs in the setting of COVID, a randomized trial is urgently needed. The aim of this trial is to assess the clinical impact of continuation vs. discontinuation of ACE inhibitors and angiotensin receptor blockers on outcomes in patients hospitalized with COVID-19.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-03-31
• Study First Submitted: 2020-04-01
• Study First Submitted QC: 2020-04-07
• Study First Posted: 2020-04-08
• Primary Completion: 2020-08-20
• Study Completion: 2020-08-20
• Results First Submitted: 2021-01-28
• Status Verified: 2021-04
• Results First Submitted QC: 2021-04-07
• Last Update Submitted: 2021-04-07
• Results First Posted: 2021-04-09
• Last Update Posted: 2021-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 152

Inclusion Criteria

1. Age 18 years or older
2. Hospitalization with a suspected diagnosis of COVID-19, based on: (a) A compatible clinical presentation with a positive laboratory test for SARS-CoV-2, or (b) Considered by the primary team to be a Person Under Investigation due to undergo testing for COVID-19 in addition to compatible pulmonary infiltrates on chest x-ray (mutilobar, intersticial or ground glass opacities).
3. Use of ACEI or ARB as an outpatient prior to hospital admission.

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Exclusion Criteria

1. Systolic blood pressure <100 mmHg.
2. Systolic blood pressure > 180 mmHg or >160 if unable to substitute ACEIs/ARBs for another antihypertensive class, per the investigator's discretion.
3. Diastolic blood pressure > 110 mmHg
4. Known history of heart failure with reduced ejection fraction (EF <40%) on their most recent echo and/or clinical heart failure with unknown EF (i.e. no echo in approximately the past year).
5. Serum K>5.0 mEq/L on admission.
6. Known pregnancy or breastfeeding.
7. eGFR <30 mL/min/1.73m2
8. >50% increase in creatinine (to a creatinine >1.5 mg/dl) compared to most recent creatinine in the past six months, if available
9. Urine protein-to-creatitine ratio > 3 g/g or proteinuria > 3 g/24-hours within the past year
10. Ongoing treatment with aliskiren or sacubitril-valsartan.
11. Inability to obtain informed consent from patient.
12. Inability to read and write or lack of access to a smart phone, computer or tablet device at the time of evaluation.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Discontinuation arm	Discontinuation of ARB/ACEI	The randomized intervention will be the discontinuation of ACEI/ARBs
Continuation arm	Continuation of ARB/ACEI	The randomized intervention will be the continuation of ACEI/ARBs

Primary Outcome Measures

Name	Time	Method
Hierarchical Composite Endpoint	Up to 28 days	The primary endpoint of the trial will be a global rank based on patient outcomes according to four factors: (1) time to death, (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), (3) the number of days supported by renal replacement therapy or pressor/inotropic therapy, and (4) a modified sequential Organ Failure Assessment (SOFA) score. The modified SOFA score will include the cardiac, respiratory, renal and coagulation domains of the SOFA score.; How to interpret the rank?: patients are ranked from worst to best outcomes, such that patients with bad outcomes are ranked at the top and patients who have the best outcomes are ranked at the bottom.

Secondary Outcome Measures

Name	Time	Method
All-Cause Death	Up to 28 days
Length of Hospital Stay	Up to 28 days	This outcome measurement looked at the median length of hospitalization.
Length of ICU Stay, Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation	Up to 28 days
AUC SOFA	Up to 28 days	The Area Under the Curve of the modified SOFA (AUC SOFA) from daily measurements, weighted to account for the shorter observation period among patients who die in-hospital.; How to interpret the AUC SOFA?: a higher area indicates more severe disease and/or longer hospitalization.The range is 0.1 to 377.3.

Trial Locations

Locations (1)

University of Pennsylvania Health System; 🇺🇸 Philadelphia, Pennsylvania, United States