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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04353596
Recruitment Status : Recruiting
First Posted : April 20, 2020
Last Update Posted : April 24, 2020
Sponsor:
Collaborator:
Ludwig-Maximilians - University of Munich
Information provided by (Responsible Party):
Medical University Innsbruck

Study Description
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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

Condition or disease Intervention/treatment Phase
SARS-CoV-2 COVID-19 Drug: ACE inhibitor, angiotensin receptor blocker Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 208 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: open-label, randomized design
Masking: Single (Outcomes Assessor)
Masking Description: unmasked
Primary Purpose: Treatment
Official Title: Stopping ACE-inhibitors in COVID-19: A Randomized Controlled Trial
Estimated Study Start Date : April 15, 2020
Estimated Primary Completion Date : May 15, 2021
Estimated Study Completion Date : May 15, 2022
Arms and Interventions
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Arm Intervention/treatment
Experimental: Stopping/replacing ACEI/ARB
Chronic treatment with ACEI or ARB will be stopped or replaced.
 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.
No Intervention: Control
No intervention, which means further treatment with ACEI or ARB.


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. Composite of admission to an intensive care unit (ICU), the use of mechanical ventilation, or all-cause death [ Time Frame: 30 days ]

Secondary Outcome Measures :
  1. 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

  2. Rates of non-invasive ventilation [ Time Frame: 30 days ]
    high-flow, continuous positive airway pressure therapy

  3. Rates of renal replacement therapies [ Time Frame: 30 days ]
  4. Change of viral burden [ Time Frame: 30 days ]
  5. 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 ]
  6. Number of patients with systolic/diastolic blood pressure > 180/120 mmHg [ Time Frame: 30 days ]
  7. Hospitalisation due to cardiac decompensation [ Time Frame: 30 days ]
    with causal relationship to stopping of ACEI/ARB therapy

  8. Rates of mechanical ventilation [ Time Frame: 30 days ]
  9. Rates of clonal hematopoiesis of indeterminate potential (CHIP) [ Time Frame: 30 days ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04353596


Contacts
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Contact: Axel Bauer, MD +4351250425621 axel.bauer@i-med.ac.at
Contact: Steffen Massberg, MD +4989440072371 steffen.massberg@med.uni-muenchen.de

Locations
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Sponsors and Collaborators
Medical University Innsbruck
Ludwig-Maximilians - University of Munich
More Information
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Responsible Party: Medical University Innsbruck
ClinicalTrials.gov Identifier: NCT04353596    
Other Study ID Numbers: EudraCT 2020-001206-35
First Posted: April 20, 2020    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Medical University Innsbruck:
ACE-inhibitors
RAS system
angiotensin receptor blockers
SARS-CoV-2
COVID-19
Additional relevant MeSH terms:
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Angiotensin-Converting Enzyme Inhibitors
Angiotensin Receptor Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action