Clinical trial NCT04374695: Renin-Angiotensin-Aldosterone System Inhibitors, Hypertension, and COVID-19
Official title: Association Between Hypertension, Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Keywords: COVID-19
Angiotensin-Converting Enzyme Inhibitors
Angiotensin Receptor Blockers
Renin-Angiotensin System
Hypertension
Observational Study
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
Collaborators: name: Bernard LIVAREK, MD, Cardiology department, Versailles Hospital
name: Jean-Paul BERESSI, MD, Department of diabetology, Versailles Hospital
name: Mehrsa KOUKABI FRADELIZZI, MD, Emergency department, Versailles Hospital
name: Floriane GILLES, MD, Cardiology department, Versailles Hospital
name: Alisson BERTRAND, Cardiology department, Versailles Hospital
name: Marie DE TOURNEMIRE, Cardiology department, Versailles Hospital
name: Victorien MONGUILLON, Cardiology department, Versailles Hospital
name: Maeva PASQUALINI, Cardiology department, Versailles Hospital
name: Alix PREVOT, Cardiology department, Versailles Hospital
name: Guillaume ROGER, Cardiology department, Versailles Hospital
name: Joseph SABA, Cardiology department, Versailles Hospital
name: Joséphine SOLTANI, Cardiology department, Versailles Hospital
name: Jean-François PROST, Cardiology department, Versailles Hospital
name: Cécile LAUREANA, Department of medical information, Versailles Hospital
First posted: 2020-05-05
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients presenting to the Centre hospitalier de Versailles emergency department from 2020 March 10th to April, 15th with clinical symptoms suggestive of COVID-19, who fulfilled the inclusion criteria.

Brief summary: Background. Angiotensing converting enzyme type 2 (ACE2), a key enzyme of the renin-angiotensin-aldosterone system (RAAS), is the receptor of SARS-CoV-2 for cell entry into lungs. Because ACE2 may be modulated by RAAS inhibitors, such as angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEi and ARBs may be at higher risk for COVID-19 infection and severity.

Aim. To analyze the associations between COVID-19 and hypertension, and treatments with ACEi and ARBs.

Methods. In this retrospective observational study, consecutive patients hospitalized for suspected COVID-19 pneumonia will be divided into 2 groups, whether or not COVID-19 is confirmed. The two groups will be compared for baseline characteristics, mainly prior treatment with ACEi and ARBs, and clinical outcome at 1-month follow-up.

The main hypothesis is that ACEi and ARBs, which interact differently with ACE2, may have different relationships with COVID-19 infection or severity.

Detailed description: The coronavirus disease 2019 (Covid-19) pandemic is currently the main challenge facing healthcare providers. Data are lacking to guide clinical decision.

The renin-angiotensin-aldosterone system (RAAS) is a key process in cardiology. Its inhibition using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type 1-receptor blockers (ARBs) is a cornerstone of the long-term management of arterial hypertension, heart failure and acute coronary syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the angiotensin-converting enzyme 2 (ACE2) as a cellular entry receptor. ACE2 is part of the RAAS and is likely to be modulated by the use of ACEi and ARBs. Therefore, there is concern that patients who are treated with ACEi and ARBs may be at higher risk for Covid-19 infection.

However, little is known regarding how ACEi and ARBs could affect Covid-19 infection and severity. First, ACE2 may have a protective effect against lung injury because it degrades angiotensin II to angiotensin-(1-7). Second, the effect of RAAS inhibition on ACE2 expression has been poorly studied in humans. Third, ACE inhibitors and ARB have different effect on the RAAS and therefore their interaction with Covid-19 may differ.

The COVHYP study is designed to address part of these issues. This is an analytical retrospective observational study that will collect and analyze data regarding patients hospitalized with suspected Covid-19. We planned to screen for inclusion all consecutive patients referred form 10/03/2020 to 15/04/2020 to the emergency department of the Versailles Hospital, a tertiary center located in greater Paris area - one of the region most affected by Covid-19 in France through this period. The inclusion criteria are as follows: 1) Clinical presentation suggestive of COVID-19 pneumonia, at least fever or influenza-like syndrome AND cough or dyspnea; and 2) Test of the presence of SARS-CoV-2 RNA by RT-PCR in nasopharyngeal or sputum samples. Two groups of patients will be defined, those with confirmed Covid-19 pneumonia, and those without Covid-19. Hospital data will gathered, and patients or relatives will be contacted by phone for a one-month follow-up. We will compare baseline characteristics of patients, especially the previous treatment by ACEi or ARBs, in the two groups of patients, and evaluate whether these characteristics can be associated with diagnosis of SARS-CoV-2 infection and severity.

We hope that this study will provide a better understanding of the effect of RAAS inhibitors on Covid-19 pneumonia and its severity.

Eligibility criteria: Inclusion Criteria:

* Age equal or more than 18;
* Symptoms suggestive of Covid-19 pneumonia. At least : fever \> 38°C or influenza-like illness (asthenia, myalgia, chills, muscular aches, ...) AND cough or dyspnea;
* Hospitalization required on clinical criteria including: oxygen saturation \<96% without oxygen support, respiratory frequency \> 25 per minute, hemodynamic instability, medical history or comorbidities known at high risk for Covid-19 (chronic heart disease, congestive heart failure, chronic bronchopulmonary disease, diabetes mellitus, age\>70, history of cancer, immunosuppression, ...);
* Covid-19 confirmation test performed (RT-PCR).

Exclusion Criteria:

* Age \< 18
* Refusal to participate in the study
* detainee or prisoner
* Protected adult uncapable to consent

Primary outcomes:
measure: Prior treatment by ACEi
timeFrame: at admission to hospital
measure: Prior treatment by ARB
timeFrame: at admission to hospital
Secondary outcomes:
measure: Baseline characteristics and comorbidities
timeFrame: at admission to hospital
measure: Major Clinical Adverse Events
timeFrame: One month follow-up
Other outcomes:
Locations:
Study officials:
References: