Stopping ACE-inhibitors in COVID-19

COVID-19 Clinical Trial

— ACEI-COVID  

Official title:

Stopping ACE-inhibitors in COVID-19: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04353596
• Other study ID #: EudraCT 2020-001206-35
• Status: Completed
• Phase: Phase 4
• Start date: April 20, 2020
• Est. completion date: February 24, 2021

Study information

• Verified date: February 2021
• Source: Medical University Innsbruck
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ACEI-COVID-19 is a multicenter, randomized trial testing the hypothesis that stopping/replacing chronic treatment with ACE-inhibitors (ACEI) or angiotensin receptor blockers (ARB) improves outcomes in symptomatic SARS-CoV2-infected patients

Description:

The COVID-19 pandemic currently poses unprecedented challenges to the health systems of all countries. Experimental studies show that the SARS-CoV2 virus enters human cells via the angiotensin converting enzyme II receptor 2 (ACE2). ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) can lead to an increase in the expression of ACE2. Therefore, there is concern that in patients treated with ACEI or ARB, the absorption of the virus is facilitated, thereby accelerating its spread in the body.

ACEI-COVID tests the hypothesis that stopping chronic ACEI / ARB therapy in SARS-CoV2-infected patients improves outcomes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: February 24, 2021
• Est. primary completion date: February 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female and male patients competent to make a decision

• Proven and symptomatic SARS-CoV2 infection = 5 days

• Patient age = 18 years

• Provided written informed consent

• Chronic (= 1 month) ACEI/ARB therapy for treatment of arterial hypertension, diabetes mellitus, heart failure or coronary artery disease

• Stable hemodynamic conditions allowing to stop or continue treatment with ACEI/ARB (systolic blood pressure =180mmHg)

Exclusion Criteria:

• Women capable of bearing children as well as pregnant and breastfeeding women

• Participant in another interventional trail

• At screening visit, no oral medication intake possible

• Advanced heart failure NYHA Stage III-IV

• Left ventricular ejection fraction <30% or NTproBNP =600pg/mL in case of clinical signs of heart failure

• Acute coronary syndrome = 3 months

• Severe arterial hypertension (concomitant use of more than 4 different antihypertensive drug classes)

• Acute respiratory distress syndrome with need for mechanical ventilation

• Patients who at not capable of home blood pressure monitoring

• Patients who cannot be switched to an alternative medication

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2

Intervention

Drug:
• ACE inhibitor, angiotensin receptor blocker
In patients randomized to stopping / replacing ACEI or ARB, it may be necessary to switch to another drug without direct effect on the RAS system. In patients, randomized to continuation, it may be needed to stop ACEI or ARB (e.g. hypotension with beginning sepsis) irrespective of the study.

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz
Austria	Landeskrankenhaus Hall	Hall In Tirol
Austria	Medical University Innsbruck, Intensive Care and Emergency Medicine Department	Innsbruck
Austria	Medical University Innsbruck, University Hospital of Internal Medicine I	Innsbruck
Austria	Medical University Innsbruck, University Hospital of Internal Medicine II	Innsbruck
Austria	Medical University Innsbruck, University Hospital of Internal Medicine III	Innsbruck	Tyrol
Austria	Medical University Innsbruck, University Hospital of Internal Medicine IV	Innsbruck
Austria	Medical University Innsbruck, University Hospital of Internal Medicine V	Innsbruck
Austria	Klinikum Klagenfurt	Klagenfurt
Austria	Bezirkskrankenhaus Kufstein	Kufstein
Austria	Klinikum Lienz	Lienz
Austria	Bezirkskrankenhaus St. Johann	Sankt Johann In Tirol
Austria	Bezirkskrankenhaus Schwaz	Schwaz
Austria	Krankenhaus St. Vinzenz Zams	Zams
Germany	University Hospital Aachen	Aachen
Germany	University Hospital Augsburg	Augsburg
Germany	Asklepios Stadtklinik Bad Tölz	Bad Tölz
Germany	Klinikum Dachau	Dachau
Germany	University Hospital Erlangen	Erlangen
Germany	University Hospital Essen	Essen
Germany	University of Freiburg	Freiburg
Germany	Klinikum Memmingen	Memmingen
Germany	Krankenhaus Mühldorf	Mühldorf
Germany	LMU Klinikum, Medizinische Klinik I	Munich	Bavaria
Germany	LMU Klinikum, Medizinische Klinik II	Munich
Germany	LMU Klinikum, Medizinische Klinik III	Munich
Germany	LMU Klinikum, Medizinische Klinik IV	Munich
Germany	München Klinik Bogenhausen und Schwabing	Munich
Germany	Rotkreuzklinikum Munich	Munich
Germany	Klinikum Rosenheim	Rosenheim
Germany	Krankenhaus Weiden	Weiden

Sponsors (3)

Lead Sponsor	Collaborator
Medical University Innsbruck	Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Ludwig-Maximilians - University of Munich

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of the Maximum Sequential Organ Failure Assessment (SOFA) Score and Death Within 30 Days	The score is calculated from six different components, each of which reflects the status of an organ system, including respiratory function, cardiovascular integrity, liver function, coagulation, renal function and neurological status. The score can range from 0 (best) to 24 (worst). In case of death, the patient was by definition assigned the maximum value of 24. Outpatients were assigned a value of 0 or 24 (in the case of death).	30 days
Primary	Composite of Admission to an Intensive Care Unit (ICU), the Use of Mechanical Ventilation, or All-cause Death	Composite of admission to ICU, mechanical ventilation, and death	30 days
Secondary	Mean of Sequential Organ Failure Assessment (SOFA) Score	minimum score is 0, maximum score is 24; higher score indicates poor outcome (death-adjusted)	30 days
Secondary	Rates of Non-invasive Ventilation	Number of Participants with Non-invasive Ventilation	30 days
Secondary	Rates of Renal Replacement Therapies		30 days
Secondary	Number of Patients With Systolic/Diastolic Blood Pressure > 180/120 mmHg		30 days
Secondary	Hospitalisation Due to Cardiac Decompensation	with causal relationship to stopping of ACEI/ARB therapy	30 days
Secondary	Rates of Mechanical Ventilation		30 days