Renin-Angiotensin System Inhibitors and COVID-19

• Conditions: COVID-19; Hypertension; Cardiovascular Diseases

• Registration Number: NCT04331574
• Lead Sponsor: Societa Italiana dell'Ipertensione Arteriosa

Brief Summary

Multicentric non-profit observational study, in patients with COVID-19 hospitalized in Italy, conducted through a pseudonymised survey.

Detailed Description

The recent SARS-CoV-2 Coronavirus pandemic and subsequent spread of the disease called COVID-19 brought back to the discussion a topic already highlighted during the SARS-CoV-4 crown-related SARS epidemic of 2002. In particular, the angiotensin converting enzyme 2 (ACE2) has been identified as a functional receptor for coronaviruses, therefore including SARS-CoV-2. ACE2 is strongly expressed in the heart and lungs. SARS-CoV-2 mainly invades alveolar epithelial cells, resulting in respiratory symptoms. These symptoms could be made more severe in the presence of increased expression of ACE2. ACE2 levels can be increased by the use of renin-angiotensin system inhibitors (RAS). This therapeutic class is particularly widespread, as it represents the most important pharmacological protection for widespread diseases such as high blood pressure, heart failure and ischemic heart disease. It is therefore possible to hypothesize that pharmacological treatment with RAS inhibitors may be associated with a more severe symptomatology and clinic than COVID-19.

However, several observations from studies on SARSCoV, which are most likely also relevant for SARS-CoV-2 seem to suggest otherwise. Indeed, it has been shown that the binding of coronavirus to ACE2 leads to downregulation of ACE2, which in turn causes an ACE / ACE2 imbalance excessive production of angiotensin by the related ACE enzyme. Angiotensin II receptor 1 (AT1R) stimulated by angiotensin causes an increase in pulmonary vascular permeability, thereby mediating an increase in lung damage. Therefore, according to this hypothesis, the upregulation of ACE2, caused by the chronic intake of AT1R and ACE Inhibitors, could be protective through two mechanisms: the first, that of blocking in the AT1 receptor; second, increasing ACE2 levels decreases ACE production of angiotensin and increases ACE2 production of angiotensin 1-7.

The quickest approach to evaluating these two opposing hypotheses is to analyze the medical records of COVID-19 patients to determine whether patients on RAS antagonist therapy have a different disease outcome than patients without the above therapy.

This research aims to verify whether the chronic intake of RAS inhibitors modifies the prevalence and severity of the clinical manifestation of COVID-19.

Study Timeline

• Study Start: 2020-03-10
• Study First Submitted: 2020-03-30
• Status Verified: 2020-04
• Study First Submitted QC: 2020-04-01
• Last Update Submitted: 2020-04-01
• Study First Posted: 2020-04-02
• Last Update Posted: 2020-04-02
• Primary Completion: 2020-04-10
• Study Completion: 2020-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

Patients affected by COVID19 referring to italian outpatient clinics or hospitals

Exclusion Criteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Numbers of COVID-19 patients enrolled that use ACE inhibitors and/or Angiotensin Receptor Blockers (ARB) as antihypertensive agents	3 months	Using anamnestic data collected from the health record of the hospital or of the general practitioner, we will count the number of COVID-19 patients enrolled that were treated with ACE Inhibitors or ARB.
Numbers of COVID-19 patients enrolled with no symptoms, with moderate symptoms or with severe symptoms of pneumoni based on the WHO specification for ARDS that also used ACE inhibitors and/or Angiotensin Receptor Blockers (ARB) as antihypertensive agents	3 months	This study want to observe whether the assumption of antihypertensive ACE inhibitors or ARB increases the severity of the clinical manifestation of COVID19

Secondary Outcome Measures

Name	Time	Method
Number and type of anthropometric and clinical parameters that associate with COVID19 and COVID-19 severity	3 months	Collecting selected data from the health record and hospital charts of the patients we will assess whether among the recorded parameters there are any that can predict COVID19 prevalence and severity

Trial Locations

Locations (1)

Spedali Civili di Brescia; 🇮🇹 Brescia, Italy