Clinical trial NCT04338009: Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019
Official title: The Randomized Elimination or Prolongation of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Coronavirus Disease 2019
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Jordana B. Cohen, MD, MSCE
name: Hanff, Thomas C., M.D., MPH
name: University of Arizona
name: Hospital Nacional Carlos Alberto Seguin Escobedo - EsSalud
name: Hospital Nacional Edgardo Rebagliati Martins
name: Hospital Español de Mendoza
name: Stanford University
name: Ottawa Hospital Research Institute
name: Hospital Civil de Guadalajara
name: Universidad Catolica Argentina
name: Caja Nacional de Salud
name: Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru
name: Karolinska Institutet
name: University of Miami
name: Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina
name: University of Michigan
name: Jesse Chittams, MS
name: Duke University
name: Vasquez, Charles R., M.D.
First posted: 2020-04-08
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Hierarchical Composite Endpoint
timeFrame: Up to 28 days
Secondary outcomes:
measure: All-Cause Death
timeFrame: Up to 28 days
measure: Length of Hospital Stay
timeFrame: Up to 28 days
measure: Length of ICU Stay, Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation
timeFrame: Up to 28 days
measure: AUC SOFA
timeFrame: Up to 28 days
Other outcomes:
measure: Intensive Care Unit Admission or Respiratory Failure Requiring Mechanical Ventilation.
timeFrame: Up to 28 days
measure: Hypotension Requiring Vasopressors, Inotropes or Mechanical Hemodynamic Support
timeFrame: Up to 28 days
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
Study officials:
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