ACE Inhibitors or ARBs Discontinuation in Context of COVID-19 Pandemic

Phase 3TerminatedNCT04329195

Assistance Publique - Hôpitaux de Paris44 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 Infection

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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)

Time frame: from day 0 to day 28 or hospital discharge

Secondary Outcomes

Primary safety endpoint: major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28

Major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28

Time frame: at day 28

Clinical status as assessed with the seven-category ordinal scale on days 7, 14 and 28.

Clinical status as assessed with the seven-category ordinal scale. The seven-category ordinal scale consisted of the following categories: 1. not hospitalized with resumption of normal activities 2. not hospitalized, but unable to resume normal activities 3. hospitalized, not requiring supplemental oxygen 4. hospitalized, requiring supplemental oxygen 5. hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both 6. hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. death.

Time frame: at days 7, 14 and 28

Number of days alive free of oxygen.

Time frame: from day 0 to day 28 or hospital discharge

Number of days alive outside hospital until day28

Number of days alive outside hospital

Time frame: at day28

Number of days alive free of intensive-care unit (ICU) admission or mechanical Ventilation (invasive or non-invasive) until day28

Ventilation (invasive or non-invasive)

Time frame: at day28

Number of days alive free of mechanical ventilation (invasive or non-invasive) until day28

Number of days alive free of mechanical ventilation (invasive or non-invasive)

Time frame: at day28

Number of days alive free of ICU admission until day28

Number of days alive free of ICU admission

Time frame: at day28

Rate of all-cause mortality at day 28

Rate of all-cause mortality

Time frame: at day 28

Rate of cardiovascular death at day 28

Rate of cardiovascular death

Time frame: at day 28

Number of days alive free of acute kidney injury until hospital discharge

Number of days alive free of acute kidney injury

Time frame: at day 28 to hospital discharge

ACE Inhibitors or ARBs Discontinuation in Context of COVID-19 Pandemic

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes