Renin-Angiotensin System Inhibitors and COVID-19 (SARS-RAS)

• ClinicalTrials.gov Identifier: NCT04331574
• Recruitment Status: Recruiting
• First Posted: April 2, 2020
• Last Update Posted: April 2, 2020
• Sponsor: Societa Italiana dell'Ipertensione Arteriosa
• Information provided by (Responsible Party): Societa Italiana dell'Ipertensione Arteriosa

Study Description

Brief Summary:

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

Condition or disease
COVID-19; Hypertension; Cardiovascular Diseases

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 Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 2000 participants
• Observational Model: Case-Only
• Time Perspective: Cross-Sectional
• Target Follow-Up Duration: 3 Months
• Official Title: Phase IV Observational Study to Associate Hypertension and Hypertensinon Treatment to COVID19
• Actual Study Start Date: March 10, 2020
• Estimated Primary Completion Date: April 10, 2020
• Estimated Study Completion Date: April 30, 2020

Groups and Cohorts

Group/Cohort
covid-19 patients; Patients with certified diagnosis of COVID-19 recruited in Italian hospitals

Outcome Measures

Primary Outcome Measures :

1. Numbers of COVID-19 patients enrolled that use ACE inhibitors and/or Angiotensin Receptor Blockers (ARB) as antihypertensive agents [ Time Frame: 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.
2. 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 [ Time Frame: 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 :

1. Number and type of anthropometric and clinical parameters that associate with COVID19 and COVID-19 severity [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

COVID-19 patients enrolled in infectious disease and resuscitation centers in Italy or in home isolation and health surveillance

Criteria

Inclusion Criteria:

Patients affected by COVID19 referring to italian outpatient clinics or hospitals

Exclusion Criteria:

-

Contacts and Locations

Contacts

Contact: Guido Iaccarino, MD, PhD; +390817464717; guiaccar@unina.it

Locations

Italy

Spedali Civili di Brescia; Recruiting

Brescia, Italy

Contact: Marialorenza Muiesan

Sponsors and Collaborators

Societa Italiana dell'Ipertensione Arteriosa

Investigators

• Study Chair: Guido Iaccarino, MD; Federico II University
• Study Director: Guido Grassi, MD; Inversity of Milan, BICOCCA
• Principal Investigator: MariaLorenza Muiesan, MD; Università degli Studi di Brescia
• Principal Investigator: Claudio Borghi, MD; University of Bologna
• Principal Investigator: Claudio Ferri, MD; University of L'Aquila
• Principal Investigator: MASSIMO VOLPE, MD; Univerity of Rome "La Sapienza"
• Principal Investigator: Leonardo Sechi; University of Udine

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Iaccarino G, Grassi G, Borghi C, Grassi D, Mancusi C, Muiesan ML, Salvetti M, Volpe M, Ferri C. Preexisting Oral Anticoagulant Therapy Ameliorates Prognosis in Hospitalized COVID-19 Patients. Front Cardiovasc Med. 2021 May 13;8:633878. doi: 10.3389/fcvm.2021.633878. eCollection 2021.

Iaccarino G, Grassi G, Borghi C, Carugo S, Fallo F, Ferri C, Giannattasio C, Grassi D, Letizia C, Mancusi C, Minuz P, Perlini S, Pucci G, Rizzoni D, Salvetti M, Sarzani R, Sechi L, Veglio F, Volpe M, Muiesan ML; SARS-RAS Investigators. Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension. PLoS One. 2020 Oct 6;15(10):e0237297. doi: 10.1371/journal.pone.0237297. eCollection 2020.

Iaccarino G, Grassi G, Borghi C, Ferri C, Salvetti M, Volpe M; SARS-RAS Investigators. Age and Multimorbidity Predict Death Among COVID-19 Patients: Results of the SARS-RAS Study of the Italian Society of Hypertension. Hypertension. 2020 Aug;76(2):366-372. doi: 10.1161/HYPERTENSIONAHA.120.15324. Epub 2020 Jun 22.

• Responsible Party: Societa Italiana dell'Ipertensione Arteriosa
• ClinicalTrials.gov Identifier: NCT04331574
• Other Study ID Numbers: SARS-RAS
• First Posted: April 2, 2020
• Last Update Posted: April 2, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Societa Italiana dell'Ipertensione Arteriosa:

risk factors; SARS; ACE Inibitors; ARB

Additional relevant MeSH terms:

Hypertension; Cardiovascular Diseases; Vascular Diseases