COVID-19SARS-RASNCT04331574
Renin-Angiotensin System Inhibitors and COVID-19
An observational study of COVID-19 and Hypertension, run by Societa Italiana dell'Ipertensione Arteriosa at 1 site in Italy.
Trial summary
Multicentric non-profit observational study, in patients with COVID-19 hospitalized in Italy, conducted through a pseudonymised survey. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- COVID-19, Hypertension, Cardiovascular Diseases
- How many people
- 2,000 participants
- Where
- 1 siteItaly
- Study dates
- 10 Mar 2020to 30 Apr 2020
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: COVID-19 patients enrolled in infectious disease and resuscitation centers in Italy or in home isolation and health surveillance
Who may be able to join
- Patients affected by COVID19 referring to italian outpatient clinics or hospitals
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Spedali Civili di Brescia
Brescia
Marialorenza Muiesan
About this study
Official title: Phase IV Observational Study to Associate Hypertension and Hypertensinon Treatment to COVID19
Multicentric non-profit observational study, in patients with COVID-19 hospitalized in Italy, conducted through a pseudonymised survey.
Read the 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.
- Conditions
- COVID-19, Hypertension, Cardiovascular Diseases
- Keywords
- risk factors, SARS, ACE Inibitors, ARB
- Medical subject headings
- COVID-19, Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| covid-19 patients | Patients with certified diagnosis of COVID-19 recruited in Italian hospitals |
What is being measured
The primary outcome is the main question the study is designed to answer.
Numbers of COVID-19 patients enrolled that use ACE inhibitors and/or Angiotensin Receptor Blockers (ARB) as antihypertensive agents
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.
Measured: 3 months
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
This study want to observe whether the assumption of antihypertensive ACE inhibitors or ARB increases the severity of the clinical manifestation of COVID19
Measured: 3 months
Secondary outcomes (1)
Number and type of anthropometric and clinical parameters that associate with COVID19 and COVID-19 severity
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
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2020
- Study start10 Mar 2020
- Primary completion10 Apr 2020 (estimated)
- Study completion30 Apr 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 2,000 participants (estimated)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- Societa Italiana dell'Ipertensione Arteriosa
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guido Iaccarino, MD, Study chair, Federico II UniversityGuido Grassi, MD, Study director, Inversity of Milan, BICOCCAMariaLorenza Muiesan, MD, Principal investigator, Università degli Studi di BresciaClaudio Borghi, MD, Principal investigator, University of BolognaClaudio Ferri, MD, Principal investigator, University of L'AquilaMASSIMO VOLPE, MD, Principal investigator, Univerity of Rome "La Sapienza"Leonardo Sechi, Principal investigator, University of Udine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04331574
- Sponsor's protocol ID
- SARS-RAS
- Acronym
- SARS-RAS
- Status last verified
- Apr 2020
- First submitted
- 30 Mar 2020
- Last updated
- 2 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34055928Iaccarino 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.
PubMed 33022004Iaccarino 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.
PubMed 32564693
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV Observational Study to Associate Hypertension and Hypertensinon Treatment to COVID19
- ClinicalTrials.gov ID
- NCT04331574
- Acronym / sponsor ID
- SARS-RAS / SARS-RAS
- Conditions
- COVID-19, Hypertension, Cardiovascular Diseases
- Keywords
- risk factors, SARS, ACE Inibitors, ARB
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Societa Italiana dell'Ipertensione ArteriosaUniversity, hospital or other
- Study start
- 10 Mar 2020 (actual)
- Primary completion
- 10 Apr 2020 (estimated)
- Study completion
- 30 Apr 2020 (estimated)
- First posted
- 2 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Target follow-up
- 3 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| covid-19 patients | – | –Patients with certified diagnosis of COVID-19 recruited in Italian hospitals |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- COVID-19 patients enrolled in infectious disease and resuscitation centers in Italy or in home isolation and health surveillance
Key inclusion criteria (1 listed)
- Patients affected by COVID19 referring to italian outpatient clinics or hospitals
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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
1 secondary outcome
Number and type of anthropometric and clinical parameters that associate with COVID19 and COVID-19 severity
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2020.
- Derived from this study: PubMed 34055928Iaccarino 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.
- Derived from this study: PubMed 33022004Iaccarino 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.
- Derived from this study: PubMed 32564693Iaccarino 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guido Iaccarino, MD study chair
Federico II University
Guido Grassi, MD study director
Inversity of Milan, BICOCCA
MariaLorenza Muiesan, MD principal investigator
Università degli Studi di Brescia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 and Hypertension, run by Societa Italiana dell'Ipertensione Arteriosa at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guido Iaccarino, MD, PhD (+390817464717, guiaccar@unina.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Numbers of COVID-19 patients enrolled that use ACE inhibitors and/or Angiotensin Receptor Blockers (ARB) as antihypertensive agents (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04331574, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2020.