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Stopping ACE-inhibitors in COVID-19 (ACEI-COVID)

Primary Purpose

SARS-CoV-2, COVID-19

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
ACE inhibitor, angiotensin receptor blocker
Sponsored by
Medical University Innsbruck
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for SARS-CoV-2 focused on measuring ACE-inhibitors, RAS system, angiotensin receptor blockers, SARS-CoV-2, COVID-19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Stopping/replacing ACEI/ARB

Control

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).
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

Secondary Outcome Measures

Mean of Sequential Organ Failure Assessment (SOFA) Score
minimum score is 0, maximum score is 24; higher score indicates poor outcome (death-adjusted)
Rates of Non-invasive Ventilation
Number of Participants with Non-invasive Ventilation
Rates of Renal Replacement Therapies
Number of Patients With Systolic/Diastolic Blood Pressure > 180/120 mmHg
Hospitalisation Due to Cardiac Decompensation
with causal relationship to stopping of ACEI/ARB therapy
Rates of Mechanical Ventilation

Full Information

First Posted
April 14, 2020
Last Updated
August 18, 2022
Sponsor
Medical University Innsbruck
Collaborators
Ludwig-Maximilians - University of Munich, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
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1. Study Identification

Unique Protocol Identification Number
NCT04353596
Brief Title
Stopping ACE-inhibitors in COVID-19
Acronym
ACEI-COVID
Official Title
Stopping ACE-inhibitors in COVID-19: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
April 20, 2020 (Actual)
Primary Completion Date
February 16, 2021 (Actual)
Study Completion Date
February 24, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University Innsbruck
Collaborators
Ludwig-Maximilians - University of Munich, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2, COVID-19
Keywords
ACE-inhibitors, RAS system, angiotensin receptor blockers, SARS-CoV-2, COVID-19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
open-label, randomized design
Masking
Outcomes Assessor
Masking Description
unmasked
Allocation
Randomized
Enrollment
216 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stopping/replacing ACEI/ARB
Arm Type
Experimental
Arm Description
Chronic treatment with ACEI or ARB will be stopped or replaced.
Arm Title
Control
Arm Type
No Intervention
Arm Description
No intervention, which means further treatment with ACEI or ARB.
Intervention Type
Drug
Intervention Name(s)
ACE inhibitor, angiotensin receptor blocker
Intervention Description
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.
Primary Outcome Measure Information:
Title
Composite of the Maximum Sequential Organ Failure Assessment (SOFA) Score and Death Within 30 Days
Description
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).
Time Frame
30 days
Title
Composite of Admission to an Intensive Care Unit (ICU), the Use of Mechanical Ventilation, or All-cause Death
Description
Composite of admission to ICU, mechanical ventilation, and death
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Mean of Sequential Organ Failure Assessment (SOFA) Score
Description
minimum score is 0, maximum score is 24; higher score indicates poor outcome (death-adjusted)
Time Frame
30 days
Title
Rates of Non-invasive Ventilation
Description
Number of Participants with Non-invasive Ventilation
Time Frame
30 days
Title
Rates of Renal Replacement Therapies
Time Frame
30 days
Title
Number of Patients With Systolic/Diastolic Blood Pressure > 180/120 mmHg
Time Frame
30 days
Title
Hospitalisation Due to Cardiac Decompensation
Description
with causal relationship to stopping of ACEI/ARB therapy
Time Frame
30 days
Title
Rates of Mechanical Ventilation
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Medical University Innsbruck, University Hospital of Internal Medicine III
City
Innsbruck
State/Province
Tyrol
ZIP/Postal Code
6020
Country
Austria
Facility Name
Medical University of Graz
City
Graz
Country
Austria
Facility Name
Landeskrankenhaus Hall
City
Hall In Tirol
Country
Austria
Facility Name
Medical University Innsbruck, Intensive Care and Emergency Medicine Department
City
Innsbruck
Country
Austria
Facility Name
Medical University Innsbruck, University Hospital of Internal Medicine II
City
Innsbruck
Country
Austria
Facility Name
Medical University Innsbruck, University Hospital of Internal Medicine IV
City
Innsbruck
Country
Austria
Facility Name
Medical University Innsbruck, University Hospital of Internal Medicine I
City
Innsbruck
Country
Austria
Facility Name
Medical University Innsbruck, University Hospital of Internal Medicine V
City
Innsbruck
Country
Austria
Facility Name
Klinikum Klagenfurt
City
Klagenfurt
Country
Austria
Facility Name
Bezirkskrankenhaus Kufstein
City
Kufstein
Country
Austria
Facility Name
Klinikum Lienz
City
Lienz
Country
Austria
Facility Name
Bezirkskrankenhaus St. Johann
City
Sankt Johann In Tirol
Country
Austria
Facility Name
Bezirkskrankenhaus Schwaz
City
Schwaz
Country
Austria
Facility Name
Krankenhaus St. Vinzenz Zams
City
Zams
Country
Austria
Facility Name
LMU Klinikum, Medizinische Klinik I
City
Munich
State/Province
Bavaria
ZIP/Postal Code
81377
Country
Germany
Facility Name
University Hospital Aachen
City
Aachen
Country
Germany
Facility Name
University Hospital Augsburg
City
Augsburg
Country
Germany
Facility Name
Asklepios Stadtklinik Bad Tölz
City
Bad Tölz
Country
Germany
Facility Name
Klinikum Dachau
City
Dachau
Country
Germany
Facility Name
University Hospital Erlangen
City
Erlangen
Country
Germany
Facility Name
University Hospital Essen
City
Essen
Country
Germany
Facility Name
University of Freiburg
City
Freiburg
Country
Germany
Facility Name
Klinikum Memmingen
City
Memmingen
Country
Germany
Facility Name
LMU Klinikum, Medizinische Klinik III
City
Munich
Country
Germany
Facility Name
LMU Klinikum, Medizinische Klinik II
City
Munich
Country
Germany
Facility Name
LMU Klinikum, Medizinische Klinik IV
City
Munich
Country
Germany
Facility Name
München Klinik Bogenhausen und Schwabing
City
Munich
Country
Germany
Facility Name
Rotkreuzklinikum Munich
City
Munich
Country
Germany
Facility Name
Krankenhaus Mühldorf
City
Mühldorf
Country
Germany
Facility Name
Klinikum Rosenheim
City
Rosenheim
Country
Germany
Facility Name
Krankenhaus Weiden
City
Weiden
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34126053
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. Erratum In: Lancet Respir Med. 2021 Aug 6;:
Results Reference
derived

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Stopping ACE-inhibitors in COVID-19

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