Stopping ACE-inhibitors in COVID-19

NCT ID: NCT04353596

Last Updated: 2022-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-20
• Study Completion Date: 2021-02-24

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.

Conditions

SARS-CoV-2; COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Stopping/replacing ACEI/ARB

Chronic treatment with ACEI or ARB will be stopped or replaced.

Group Type: EXPERIMENTAL

ACE inhibitor, angiotensin receptor blocker

Intervention Type: DRUG

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.

Control

No intervention, which means further treatment with ACEI or ARB.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: collaborator

Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

OTHER

Sponsor Role: collaborator

Medical University Innsbruck

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Medical University Innsbruck, University Hospital of Internal Medicine III

Innsbruck, Tyrol, 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 II

Innsbruck, , Austria

Medical University Innsbruck, University Hospital of Internal Medicine IV

Innsbruck, , Austria

Medical University Innsbruck, University Hospital of Internal Medicine I

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, , Austria

LMU Klinikum, Medizinische Klinik I

Munich, Bavaria, 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 im Breisgau, , Germany

Klinikum Memmingen

Memmingen, , Germany

LMU Klinikum, Medizinische Klinik III

Munich, , Germany

LMU Klinikum, Medizinische Klinik II

Munich, , Germany

LMU Klinikum, Medizinische Klinik IV

Munich, , Germany

München Klinik Bogenhausen und Schwabing

Munich, , Germany

Rotkreuzklinikum Munich

Munich, , Germany

Krankenhaus Mühldorf

Mühldorf, , Germany

Klinikum Rosenheim

Rosenheim, , Germany

Krankenhaus Weiden

Weiden, , Germany

Countries

Austria; Germany

References

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.

Reference Type: DERIVED

PMID: 34126053 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

EudraCT 2020-001206-35

Identifier Type: -

Identifier Source: org_study_id