ACE Inhibitors or ARBs Discontinuation in Context of COVID-19 Pandemic (ACORES-2)

• ClinicalTrials.gov Identifier: NCT04329195
• Recruitment Status: Terminated
• First Posted: April 1, 2020
• Last Update Posted: April 9, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Groupe Hospitalier Pitié-Salpêtrière
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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.

Condition or disease	Intervention/treatment	Phase
History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 Infection	Drug: 1: discontinuation of RAS blocker therapy; Drug: 2: continuation of RAS blocker therapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 9, 2020
• Actual Primary Completion Date: December 9, 2020
• Actual Study Completion Date: January 9, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1: discontinuation of RAS blocker therapy; discontinuation of RAS blocker therapy	Drug: 1: discontinuation of RAS blocker therapy; discontinuation of RAS blocker therapy; Other Name: discontinuation of RAS blocker therapy
Active Comparator: 2: continuation of RAS blocker therapy; continuation of RAS blocker therapy	Drug: 2: continuation of RAS blocker therapy; continuation of RAS blocker therapy; Other Name: continuation of RAS blocker therapy

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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)

Secondary Outcome Measures :

1. Primary safety endpoint: 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 ]
   Major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28
2. Clinical status as assessed with the seven-category ordinal scale on days 7, 14 and 28. [ Time Frame: at 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.
3. Number of days alive free of oxygen. [ Time Frame: from day 0 to day 28 or hospital discharge ]
   Number of days alive free of oxygen.
4. Number of days alive outside hospital until day28 [ Time Frame: at day28 ]
   Number of days alive outside hospital
5. Number of days alive free of intensive-care unit (ICU) admission or mechanical Ventilation (invasive or non-invasive) until day28 [ Time Frame: at day28 ]
   Ventilation (invasive or non-invasive)
6. Number of days alive free of mechanical ventilation (invasive or non-invasive) until day28 [ Time Frame: at day28 ]
   Number of days alive free of mechanical ventilation (invasive or non-invasive)
7. Number of days alive free of ICU admission until day28 [ Time Frame: at day28 ]
   Number of days alive free of ICU admission
8. Rate of all-cause mortality at day 28 [ Time Frame: at day 28 ]
   Rate of all-cause mortality
9. Rate of cardiovascular death at day 28 [ Time Frame: at day 28 ]
   Rate of cardiovascular death
10. Number of days alive free of acute kidney injury until hospital discharge [ Time Frame: at day 28 to hospital discharge ]
    Number of days alive free of acute kidney injury

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

France

Cardiologie, Groupe Hospitalier Pitié-Salpêtrière

Paris, France, 75013

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Groupe Hospitalier Pitié-Salpêtrière

Investigators

• Principal Investigator: Gilles MONTALESCOT, MD, PhD; Institut Cardiologie - Pitié Salpêtrière(APHP) / ACTION Study Group / Univ. Paris 6 (UPMC) - INSERM UMRS 1166

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04329195
• Other Study ID Numbers: APHP200409
• First Posted: April 1, 2020
• Last Update Posted: April 9, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

SARS-CoV-2; Cardiovascular disease; RAS blockers

Additional relevant MeSH terms:

Infections; COVID-19; Cardiovascular Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases