N/A
N=152
Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019
COVID-19
Bottom Line
View on ClinicalTrials.gov: NCT04338009 ↗Enrolled (actual)
152
Serious AEs
37.5%
Results posted
Apr 2021
Primary outcome: Primary: Hierarchical Composite Endpoint — 81; 73 score on a scale (range 1 to 152)
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Discontinuation of ARB/ACEI (Other); Continuation of ARB/ACEI (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Pennsylvania
- Primary completion
- Aug 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Hierarchical Composite Endpoint |
81; 73 | — |
| SECONDARY All-Cause Death |
10; 11 | — |
| SECONDARY Length of Hospital Stay |
5; 6 | — |
| SECONDARY Length of ICU Stay, Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation |
15; 13 | — |
| SECONDARY AUC SOFA |
7; 12 | — |
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
- Age 18 years or older
- 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).
- Use of ACEI or ARB as an outpatient prior to hospital admission.
Exclusion Criteria
- Systolic blood pressure 180 mmHg or >160 if unable to substitute ACEIs/ARBs for another antihypertensive class, per the investigator's discretion.
- Diastolic blood pressure > 110 mmHg
- Known history of heart failure with reduced ejection fraction (EF 5.0 mEq/L on admission.
- Known pregnancy or breastfeeding.
- eGFR 50% increase in creatinine (to a creatinine >1.5 mg/dl) compared to most recent creatinine in the past six months, if available
- Urine protein-to-creatitine ratio > 3 g/g or proteinuria > 3 g/24-hours within the past year
- Ongoing treatment with aliskiren or sacubitril-valsartan.
- Inability to obtain informed consent from patient.
- Inability to read and write or lack of access to a smart phone, computer or tablet device at the time of evaluation.
Data sourced from ClinicalTrials.gov (NCT04338009). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.