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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04353596
Recruitment Status : Completed
First Posted : April 20, 2020
Last Update Posted : March 2, 2021
Sponsor:
Collaborators:
Ludwig-Maximilians - University of Munich
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
Information provided by (Responsible Party):
Medical University Innsbruck

Tracking Information
First Submitted Date  ICMJE April 14, 2020
First Posted Date  ICMJE April 20, 2020
Last Update Posted Date March 2, 2021
Actual Study Start Date  ICMJE April 20, 2020
Actual Primary Completion Date February 16, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2021)
  • Combination of maximum Sequential Organ Failure Assessment (SOFA) Score and death [ Time Frame: 30 days ]
    The minimal value of the SOFA Score will be 0 and the maximal value 24 points. All-cause death is classified as the maximum score (24 points). In case of a subclinical disease progress without need for hospitalization, the SOFA score will be 0.
  • Composite of admission to an intensive care unit (ICU), the use of mechanical ventilation, or all-cause death [ Time Frame: 30 days ]
    will be hierarchically tested after enrollment of 798 patients
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2020)
  • Combination of maximum Sequential Organ Failure Assessment (SOFA) Score and death [ Time Frame: 30 days ]
    The minimal value of the SOFA Score will be 0 and the maximal value 24 points. All-cause death is classified as the maximum score (24 points). In case of a subclinical disease progress without need for hospitalization, the SOFA score will be 0.
  • Composite of admission to an intensive care unit (ICU), the use of mechanical ventilation, or all-cause death [ Time Frame: 30 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2021)
  • Mean and area under the curve of Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: 30 days ]
    minimum score is 0, maximum score is 24; higher score indicates poor outcome (death-adjusted)
  • Rates of non-invasive ventilation [ Time Frame: 30 days ]
    high-flow, continuous positive airway pressure therapy
  • Rates of renal replacement therapies [ Time Frame: 30 days ]
  • Change of viral burden [ Time Frame: 30 days ]
  • Change of C-reactive protein (CRP), interleukin 6 (IL-6), D-Dimer, IL-6, hochsensitives Troponin (hsTN), NT-pro-brain natriuretic peptide (NT-pro BNP) [ Time Frame: 30 days ]
  • Number of patients with systolic/diastolic blood pressure > 180/120 mmHg [ Time Frame: 30 days ]
  • Hospitalisation due to cardiac decompensation [ Time Frame: 30 days ]
    with causal relationship to stopping of ACEI/ARB therapy
  • Rates of mechanical ventilation [ Time Frame: 30 days ]
  • Rates of clonal hematopoiesis of indeterminate potential (CHIP) [ Time Frame: 30 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2020)
  • Maximum and median maximum Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: 30 days ]
    minimum score is 0, maximum score is 24; higher score indicates poor outcome
  • Rates of non-invasive ventilation [ Time Frame: 30 days ]
    high-flow, continuous positive airway pressure therapy
  • Rates of renal replacement therapies [ Time Frame: 30 days ]
  • Change of viral burden [ Time Frame: 30 days ]
  • Change of C-reactive protein (CRP), interleukin 6 (IL-6), D-Dimer, IL-6, hochsensitives Troponin (hsTN), NT-pro-brain natriuretic peptide (NT-pro BNP) [ Time Frame: 30 days ]
  • Number of patients with systolic/diastolic blood pressure > 180/120 mmHg [ Time Frame: 30 days ]
  • Hospitalisation due to cardiac decompensation [ Time Frame: 30 days ]
    with causal relationship to stopping of ACEI/ARB therapy
  • Rates of mechanical ventilation [ Time Frame: 30 days ]
  • Rates of clonal hematopoiesis of indeterminate potential (CHIP) [ Time Frame: 30 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Stopping ACE-inhibitors in COVID-19
Official Title  ICMJE Stopping ACE-inhibitors in COVID-19: A Randomized Controlled Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
open-label, randomized design
Masking: Single (Outcomes Assessor)
Masking Description:
unmasked
Primary Purpose: Treatment
Condition  ICMJE
  • SARS-CoV-2
  • COVID-19
Intervention  ICMJE 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.
Study Arms  ICMJE
  • Experimental: Stopping/replacing ACEI/ARB
    Chronic treatment with ACEI or ARB will be stopped or replaced.
    Intervention: Drug: ACE inhibitor, angiotensin receptor blocker
  • No Intervention: Control
    No intervention, which means further treatment with ACEI or ARB.
Publications * 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, Gänzer H, von Bary C, May AE, Wöll E, von Scheidt W, Rassaf T, Duerschmied D, Brenner C, Kääb 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 Stülpnagel 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;:.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 25, 2021)
216
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2020)
208
Actual Study Completion Date  ICMJE February 24, 2021
Actual Primary Completion Date February 16, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04353596
Other Study ID Numbers  ICMJE EudraCT 2020-001206-35
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Medical University Innsbruck
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Medical University Innsbruck
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Ludwig-Maximilians - University of Munich
  • Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
Investigators  ICMJE Not Provided
PRS Account Medical University Innsbruck
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP