ACE Inhibitors or ARBs Discontinuation in Context of COVID-19 Pandemic

Study Overview
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Brief Summary
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Since December 2019, a novel coronavirus called SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused an international outbreak of respiratory illness described as COVID-19. Individuals with a history of cardiovascular disease develop a more severe illness and have higher rates of death. Because of the potential interaction between RAS blockers and SARS-CoV-2 mechanism of infection, there are ongoing scientific discussions on whether they should be stopped or continued in patients with COVID-19. It is crucial to determine whether RAS blockers should be discontinued or not in patients with COVID-19.

Official Title
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ACE Inhibitors or ARBs Discontinuation for Clinical Outcome Risk Reduction in Patients Hospitalized for the Endemic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Infection: the Randomized ACORES-2 Study

Conditions
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History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 Infection

Intervention / Treatment
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* Drug: 1: discontinuation of RAS blocker therapy
* Drug: 2: continuation of RAS blocker therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old. Chronically treated with RAS blockers (ACE inhibitors or ARBs on the last prescription prior to admission with a treatment duration ≥ 1 month). Diagnosis of COVID-19 confirmed by the presence of SARS-CoV-2 on any biological sample with any detection method. Patients hospitalized in a non-intensive care unit. Pregnancy test at inclusion visit for women of childbearing potential. Women of childbearing potential must agree to use adequate contraception according to recommendations related to contraception and pregnancy testing in clinical trials, by Clinical Trial Facilitation Group (CTFG). Exclusion Criteria: Shock requiring vasoactive agents. Acute respiratory distress syndrome requiring invasive mechanical ventilation. Circulatory assistance. History of malignant hypertension according to the definition of the 2018 ESC/ESH guidelines on hypertension. Uncontrolled blood pressure despite the use of five antihypertensive drugs. History of nephrotic syndrome. History of hospitalization for hemorrhagic stroke in the past 3 months. RAS blockers therapy previously stopped > 48h. No affiliation to the French Health Care System Sécurité Sociale. Inability to obtain informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: discontinuation of RAS blocker therapy<br>discontinuation of RAS blocker therapy | Drug: 1: discontinuation of RAS blocker therapy<br>* discontinuation of RAS blocker therapy<br>* Other names: discontinuation of RAS blocker therapy;|
| Active Comparator: 2: continuation of RAS blocker therapy<br>continuation of RAS blocker therapy | Drug: 2: continuation of RAS blocker therapy<br>* continuation of RAS blocker therapy<br>* Other names: continuation of RAS blocker therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical improvement from day 0 to day 28 (improvement of two points on a seven-category ordinal scale, or live discharge from the hospital, whichever comes first) | Time to clinical improvement from day 0 to day 28 (improvement of two points on a seven-category ordinal scale, or live discharge from the hospital, whichever comes first) | from day 0 to day 28 or hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary safety endpoint: major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28 | Major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28 | at day 28 | 
| Clinical status as assessed with the seven-category ordinal scale on days 7, 14 and 28. | Clinical status as assessed with the seven-category ordinal scale. The seven-category ordinal scale consisted of the following categories: not hospitalized with resumption of normal activities not hospitalized, but unable to resume normal activities hospitalized, not requiring supplemental oxygen hospitalized, requiring supplemental oxygen hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both hospitalized, requiring ECMO, invasive mechanical ventilation, or both death. | at days 7, 14 and 28 | 
| Number of days alive free of oxygen. | Number of days alive free of oxygen. | from day 0 to day 28 or hospital discharge | 
| Number of days alive outside hospital until day28 | Number of days alive outside hospital | at day28 | 
| Number of days alive free of intensive-care unit (ICU) admission or mechanical Ventilation (invasive or non-invasive) until day28 | Ventilation (invasive or non-invasive) | at day28 | 
| Number of days alive free of mechanical ventilation (invasive or non-invasive) until day28 | Number of days alive free of mechanical ventilation (invasive or non-invasive) | at day28 | 
| Number of days alive free of ICU admission until day28 | Number of days alive free of ICU admission | at day28 | 
| Rate of all-cause mortality at day 28 | Rate of all-cause mortality | at day 28 | 
| Rate of cardiovascular death at day 28 | Rate of cardiovascular death | at day 28 | 
| Number of days alive free of acute kidney injury until hospital discharge | Number of days alive free of acute kidney injury | at day 28 to hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, RAS blockers, Cardiovascular disease