History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 InfectionPhase 3ACORES-2NCT04329195
ACE Inhibitors or ARBs Discontinuation in Context of COVID-19 Pandemic
A Phase 3 study testing 1: discontinuation of RAS blocker therapy and 2: continuation of RAS blocker therapy in people with History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 Infection
- What is being tested?
- 1: discontinuation of RAS blocker therapy and 2: continuation of RAS blocker therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteFrance
- Study dates
- 9 Apr 2020to 9 Jan 2021
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Being tested
- 1: discontinuation of RAS blocker therapy, 2: continuation of RAS blocker therapy
- Keywords
- SARS-CoV-2, Cardiovascular disease, RAS blockers
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1: discontinuation of RAS blocker therapyDrug
Also called discontinuation of RAS blocker therapy
discontinuation of RAS blocker therapy
2: continuation of RAS blocker therapyDrug
Also called continuation of RAS blocker therapy
continuation of RAS blocker therapy
| Study group | Role | What they receive |
|---|---|---|
| 1: discontinuation of RAS blocker therapy | Experimental | discontinuation of RAS blocker therapy Receives: Drug: 1: discontinuation of RAS blocker therapy |
| 2: continuation of RAS blocker therapy | Active comparator | continuation of RAS blocker therapy Receives: Drug: 2: continuation of RAS blocker therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 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)
Measured: from day 0 to day 28 or hospital discharge
Secondary outcomes (10)
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
Measured: 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:
- not hospitalized with resumption of normal activities
- not hospitalized, but unable to resume normal activities
- hospitalized, not requiring supplemental oxygen
- hospitalized, requiring supplemental oxygen
- hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both
- hospitalized, requiring ECMO, invasive mechanical ventilation, or both
- death.
Measured: at days 7, 14 and 28
Number of days alive free of oxygen.
Number of days alive free of oxygen.
Measured: from day 0 to day 28 or hospital discharge
Number of days alive outside hospital until day28
Number of days alive outside hospital
Measured: 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)
Measured: 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)
Measured: at day28
Number of days alive free of ICU admission until day28
Number of days alive free of ICU admission
Measured: at day28
Rate of all-cause mortality at day 28
Rate of all-cause mortality
Measured: at day 28
Rate of cardiovascular death at day 28
Rate of cardiovascular death
Measured: at day 28
Number of days alive free of acute kidney injury until hospital discharge
Number of days alive free of acute kidney injury
Measured: at day 28 to hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start9 Apr 2020
- Primary completion9 Dec 2020
- Study completion9 Jan 2021
Why it stopped: insufficient recrutment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 InfectionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Groupe Hospitalier Pitie-Salpetriere
- Responsible party
- Sponsor
- Investigators
- Gilles MONTALESCOT, MD, PhD, Principal investigator, Institut Cardiologie - Pitié Salpêtrière(APHP) / ACTION Study Group / Univ. Paris 6 (UPMC) - INSERM UMRS 1166
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04329195
- Sponsor's protocol ID
- APHP200409
- Acronym
- ACORES-2
- Status last verified
- Apr 2021
- First submitted
- 28 Mar 2020
- Last updated
- 9 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04329195
- Acronym / sponsor ID
- ACORES-2 / APHP200409
- Keywords
- SARS-CoV-2, Cardiovascular disease, RAS blockers
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient recrutment
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Groupe Hospitalier Pitie-Salpetriere
- Study start
- 9 Apr 2020 (actual)
- Primary completion
- 9 Dec 2020 (actual)
- Study completion
- 9 Jan 2021 (actual)
- First posted
- 1 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: discontinuation of RAS blocker therapy | Experimental | Drug: 1: discontinuation of RAS blocker therapydiscontinuation of RAS blocker therapy |
| 2: continuation of RAS blocker therapy | Active comparator | Drug: 2: continuation of RAS blocker therapycontinuation of RAS blocker therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1: discontinuation of RAS blocker therapyAlso: discontinuation of RAS blocker therapydiscontinuation of RAS blocker therapy | Drug | 1: discontinuation of RAS blocker therapy |
| 2: continuation of RAS blocker therapyAlso: continuation of RAS blocker therapycontinuation of RAS blocker therapy | Drug | 2: continuation of RAS blocker therapy |
Primary outcome
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)
10 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
Time frame: at day 28
Clinical status as assessed with the seven-category ordinal scale on days 7, 14 and 28.
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
Time frame: at day28
Number of days alive free of intensive-care unit (ICU) admission or mechanical Ventilation (invasive or non-invasive) until day28
Time frame: at day28
Number of days alive free of mechanical ventilation (invasive or non-invasive) until day28
Time frame: at day28
Number of days alive free of ICU admission until day28
Time frame: at day28
Rate of all-cause mortality at day 28
Time frame: at day 28
Rate of cardiovascular death at day 28
Time frame: at day 28
Number of days alive free of acute kidney injury until hospital discharge
Time frame: at day 28 to hospital discharge
Results and safety
The study was stopped early (reason given: insufficient recrutment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2021.
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.
Gilles MONTALESCOT, MD, PhD principal investigator
Institut Cardiologie - Pitié Salpêtrière(APHP) / ACTION Study Group / Univ. Paris 6 (UPMC) - INSERM UMRS 1166
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 1: discontinuation of RAS blocker therapy and 2: continuation of RAS blocker therapy in people with History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 6 inclusion and 10 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: stopped early, as of the sponsor's last update on 9 Apr 2021. 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 France. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: insufficient recrutment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: from day 0 to day 28 or hospital discharge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Apr 2021.