Clinical trial NCT04353596: Stopping ACE-inhibitors in COVID-19
Official title: Stopping ACE-inhibitors in COVID-19: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: SARS-CoV-2
COVID-19
Keywords: ACE-inhibitors
RAS system
angiotensin receptor blockers
SARS-CoV-2
COVID-19
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
Collaborators: name: Ludwig-Maximilians - University of Munich
name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
First posted: 2020-04-20
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: open-label, randomized design
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite of the Maximum Sequential Organ Failure Assessment (SOFA) Score and Death Within 30 Days
timeFrame: 30 days
measure: Composite of Admission to an Intensive Care Unit (ICU), the Use of Mechanical Ventilation, or All-cause Death
timeFrame: 30 days
Secondary outcomes:
measure: Mean of Sequential Organ Failure Assessment (SOFA) Score
timeFrame: 30 days
measure: Rates of Non-invasive Ventilation
timeFrame: 30 days
measure: Rates of Renal Replacement Therapies
timeFrame: 30 days
measure: Number of Patients With Systolic/Diastolic Blood Pressure > 180/120 mmHg
timeFrame: 30 days
measure: Hospitalisation Due to Cardiac Decompensation
timeFrame: 30 days
measure: Rates of Mechanical Ventilation
timeFrame: 30 days
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, University Hospital of Internal Medicine III
state: Tyrol
city: Graz
country: Austria
facility: Medical University of Graz
city: Hall In Tirol
country: Austria
facility: Landeskrankenhaus Hall
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Intensive Care and Emergency Medicine Department
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, University Hospital of Internal Medicine II
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, University Hospital of Internal Medicine IV
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, University Hospital of Internal Medicine I
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, University Hospital of Internal Medicine V
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt
city: Kufstein
country: Austria
facility: Bezirkskrankenhaus Kufstein
city: Lienz
country: Austria
facility: Klinikum Lienz
city: Sankt Johann In Tirol
country: Austria
facility: Bezirkskrankenhaus St. Johann
city: Schwaz
country: Austria
facility: Bezirkskrankenhaus Schwaz
city: Zams
country: Austria
facility: Krankenhaus St. Vinzenz Zams
city: Munich
country: Germany
facility: LMU Klinikum, Medizinische Klinik I
state: Bavaria
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Augsburg
country: Germany
facility: University Hospital Augsburg
city: Bad Tölz
country: Germany
facility: Asklepios Stadtklinik Bad Tölz
city: Dachau
country: Germany
facility: Klinikum Dachau
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Essen
country: Germany
facility: University Hospital Essen
city: Freiburg
country: Germany
facility: University of Freiburg
city: Memmingen
country: Germany
facility: Klinikum Memmingen
city: Munich
country: Germany
facility: LMU Klinikum, Medizinische Klinik III
city: Munich
country: Germany
facility: LMU Klinikum, Medizinische Klinik II
city: Munich
country: Germany
facility: LMU Klinikum, Medizinische Klinik IV
city: Munich
country: Germany
facility: München Klinik Bogenhausen und Schwabing
city: Munich
country: Germany
facility: Rotkreuzklinikum Munich
city: Mühldorf
country: Germany
facility: Krankenhaus Mühldorf
city: Rosenheim
country: Germany
facility: Klinikum Rosenheim
city: Weiden
country: Germany
facility: Krankenhaus Weiden
Study officials:
References:
citation: Bauer A, Schreinlechner M, Sappler N, Dolejsi T, Tilg H, Aulinger BA, Weiss G, Bellmann-Weiler R, Adolf C, Wolf D, Pirklbauer M, Graziadei I, Ganzer H, von Bary C, May AE, Woll E, von Scheidt W, Rassaf T, Duerschmied D, Brenner C, Kaab S, Metzler B, Joannidis M, Kain HU, Kaiser N, Schwinger R, Witzenbichler B, Alber H, Straube F, Hartmann N, Achenbach S, von Bergwelt-Baildon M, von Stulpnagel L, Schoenherr S, Forer L, Embacher-Aichhorn S, Mansmann U, Rizas KD, Massberg S; ACEI-COVID investigators. Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial. Lancet Respir Med. 2021 Aug;9(8):863-872. doi: 10.1016/S2213-2600(21)00214-9. Epub 2021 Jun 11.