Clinical trial NCT04331574: Renin-Angiotensin System Inhibitors and COVID-19
Official title: Phase IV Observational Study to Associate Hypertension and Hypertensinon Treatment to COVID19
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Hypertension
Cardiovascular Diseases
Keywords: risk factors
SARS
ACE Inibitors
ARB
Lead sponsor: Societa Italiana dell'Ipertensione Arteriosa
Sponsor class: OTHER
First posted: 2020-04-02
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
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

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.

Eligibility criteria: Inclusion Criteria:

Patients affected by COVID19 referring to italian outpatient clinics or hospitals

Exclusion Criteria:

-

Primary outcomes:
measure: Numbers of COVID-19 patients enrolled that use ACE inhibitors and/or Angiotensin Receptor Blockers (ARB) as antihypertensive agents
timeFrame: 3 months
measure: 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
timeFrame: 3 months
Secondary outcomes:
measure: Number and type of anthropometric and clinical parameters that associate with COVID19 and COVID-19 severity
timeFrame: 3 months
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
Study officials:
affiliation: Federico II University
name: Guido Iaccarino, MD
role: STUDY_CHAIR
affiliation: Inversity of Milan, BICOCCA
name: Guido Grassi, MD
role: STUDY_DIRECTOR
affiliation: Università degli Studi di Brescia
name: MariaLorenza Muiesan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Bologna
name: Claudio Borghi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of L'Aquila
name: Claudio Ferri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Univerity of Rome "La Sapienza"
name: MASSIMO VOLPE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Udine
name: Leonardo Sechi
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.