Stopping ACE-inhibitors in COVID-19

Study Overview
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Brief Summary
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ACEI-COVID-19 is a multicenter, randomized trial testing the hypothesis that stopping/replacing chronic treatment with ACE-inhibitors (ACEI) or angiotensin receptor blockers (ARB) improves outcomes in symptomatic SARS-CoV2-infected patients

Detailed Description
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The COVID-19 pandemic currently poses unprecedented challenges to the health systems of all countries. Experimental studies show that the SARS-CoV2 virus enters human cells via the angiotensin converting enzyme II receptor 2 (ACE2). ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) can lead to an increase in the expression of ACE2. Therefore, there is concern that in patients treated with ACEI or ARB, the absorption of the virus is facilitated, thereby accelerating its spread in the body. ACEI-COVID tests the hypothesis that stopping chronic ACEI / ARB therapy in SARS-CoV2-infected patients improves outcomes.

Official Title
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Stopping ACE-inhibitors in COVID-19: A Randomized Controlled Trial

Conditions
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SARS-CoV-2, COVID-19

Intervention / Treatment
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* Drug: ACE inhibitor, angiotensin receptor blocker


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male patients competent to make a decision Proven and symptomatic SARS-CoV2 infection ≤ 5 days Patient age ≥ 18 years Provided written informed consent Chronic (≥ 1 month) ACEI/ARB therapy for treatment of arterial hypertension, diabetes mellitus, heart failure or coronary artery disease Stable hemodynamic conditions allowing to stop or continue treatment with ACEI/ARB (systolic blood pressure ≤180mmHg) Exclusion Criteria: Women capable of bearing children as well as pregnant and breastfeeding women Participant in another interventional trail At screening visit, no oral medication intake possible Advanced heart failure NYHA Stage III-IV Left ventricular ejection fraction <30% or NTproBNP ≥600pg/mL in case of clinical signs of heart failure Acute coronary syndrome ≤ 3 months Severe arterial hypertension (concomitant use of more than 4 different antihypertensive drug classes) Acute respiratory distress syndrome with need for mechanical ventilation Patients who at not capable of home blood pressure monitoring Patients who cannot be switched to an alternative medication

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
Interventional Model Description: open-label, randomized design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stopping/replacing ACEI/ARB<br>Chronic treatment with ACEI or ARB will be stopped or replaced. | Drug: ACE inhibitor, angiotensin receptor blocker<br>* In patients randomized to stopping / replacing ACEI or ARB, it may be necessary to switch to another drug without direct effect on the RAS system. In patients, randomized to continuation, it may be needed to stop ACEI or ARB (e.g. hypotension with beginning sepsis) irrespective of the study.<br>|
| No Intervention: Control<br>No intervention, which means further treatment with ACEI or ARB. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of the Maximum Sequential Organ Failure Assessment (SOFA) Score and Death Within 30 Days | The score is calculated from six different components, each of which reflects the status of an organ system, including respiratory function, cardiovascular integrity, liver function, coagulation, renal function and neurological status. The score can range from 0 (best) to 24 (worst). In case of death, the patient was by definition assigned the maximum value of 24. Outpatients were assigned a value of 0 or 24 (in the case of death). | 30 days | 
| Composite of Admission to an Intensive Care Unit (ICU), the Use of Mechanical Ventilation, or All-cause Death | Composite of admission to ICU, mechanical ventilation, and death | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of Sequential Organ Failure Assessment (SOFA) Score | minimum score is 0, maximum score is 24; higher score indicates poor outcome (death-adjusted) | 30 days | 
| Rates of Non-invasive Ventilation | Number of Participants with Non-invasive Ventilation | 30 days | 
| Rates of Renal Replacement Therapies |  | 30 days | 
| Number of Patients With Systolic/Diastolic Blood Pressure > 180/120 mmHg |  | 30 days | 
| Hospitalisation Due to Cardiac Decompensation | with causal relationship to stopping of ACEI/ARB therapy | 30 days | 
| Rates of Mechanical Ventilation |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACE-inhibitors, RAS system, angiotensin receptor blockers, SARS-CoV-2, COVID-19