Clinical trial NCT04329195: ACE Inhibitors or ARBs Discontinuation in Context of COVID-19 Pandemic
Official title: ACE Inhibitors or ARBs Discontinuation for Clinical Outcome Risk Reduction in Patients Hospitalized for the Endemic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Infection: the Randomized ACORES-2 Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 Infection
Keywords: SARS-CoV-2
Cardiovascular disease
RAS blockers
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Groupe Hospitalier Pitié-Salpêtrière
First posted: 2020-04-01
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Since December 2019, a novel coronavirus called SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused an international outbreak of respiratory illness described as COVID-19.

Individuals with a history of cardiovascular disease develop a more severe illness and have higher rates of death.

Because of the potential interaction between RAS blockers and SARS-CoV-2 mechanism of infection, there are ongoing scientific discussions on whether they should be stopped or continued in patients with COVID-19.

It is crucial to determine whether RAS blockers should be discontinued or not in patients with COVID-19.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old.
* Chronically treated with RAS blockers (ACE inhibitors or ARBs on the last prescription prior to admission with a treatment duration ≥ 1 month).
* Diagnosis of COVID-19 confirmed by the presence of SARS-CoV-2 on any biological sample with any detection method.
* Patients hospitalized in a non-intensive care unit.
* Pregnancy test at inclusion visit for women of childbearing potential.
* Women of childbearing potential must agree to use adequate contraception according to recommendations related to contraception and pregnancy testing in clinical trials, by Clinical Trial Facilitation Group (CTFG).

Exclusion Criteria:

* Shock requiring vasoactive agents.
* Acute respiratory distress syndrome requiring invasive mechanical ventilation.
* Circulatory assistance.
* History of malignant hypertension according to the definition of the 2018 ESC/ESH guidelines on hypertension.
* Uncontrolled blood pressure despite the use of five antihypertensive drugs.
* History of nephrotic syndrome.
* History of hospitalization for hemorrhagic stroke in the past 3 months.
* RAS blockers therapy previously stopped \> 48h.
* No affiliation to the French Health Care System "Sécurité Sociale".
* Inability to obtain informed consent.

Primary outcomes:
measure: Time to clinical improvement from day 0 to day 28 (improvement of two points on a seven-category ordinal scale, or live discharge from the hospital, whichever comes first)
timeFrame: from day 0 to day 28 or hospital discharge
Secondary outcomes:
measure: Primary safety endpoint: major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28
timeFrame: at day 28
measure: Clinical status as assessed with the seven-category ordinal scale on days 7, 14 and 28.
timeFrame: at days 7, 14 and 28
measure: Number of days alive free of oxygen.
timeFrame: from day 0 to day 28 or hospital discharge
measure: Number of days alive outside hospital until day28
timeFrame: at day28
measure: Number of days alive free of intensive-care unit (ICU) admission or mechanical Ventilation (invasive or non-invasive) until day28
timeFrame: at day28
measure: Number of days alive free of mechanical ventilation (invasive or non-invasive) until day28
timeFrame: at day28
measure: Number of days alive free of ICU admission until day28
timeFrame: at day28
measure: Rate of all-cause mortality at day 28
timeFrame: at day 28
measure: Rate of cardiovascular death at day 28
timeFrame: at day 28
measure: Number of days alive free of acute kidney injury until hospital discharge
timeFrame: at day 28 to hospital discharge
Other outcomes:
Locations:
city: Paris
country: France
facility: Cardiologie, Groupe Hospitalier Pitié-Salpêtrière
Study officials:
affiliation: Institut Cardiologie - Pitié Salpêtrière(APHP) / ACTION Study Group / Univ. Paris 6 (UPMC) - INSERM UMRS 1166
name: Gilles MONTALESCOT, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: