ACEI-COVID: Stopping ACE-inhibitors in COVID-19

Sponsor

Medical University Innsbruck (Other)

Overall Status

Completed

CT.gov ID

NCT04353596

Collaborator

Ludwig-Maximilians - University of Munich (Other), Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) (Other)

216

Enrollment

Locations

Arms

10.2

Actual Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

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

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

Study Type:

Interventional

Actual Enrollment :

216 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

open-label, randomized designopen-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

Actual Study Start Date :

Apr 20, 2020

Actual Primary Completion Date :

Feb 16, 2021

Actual Study Completion Date :

Feb 24, 2021

Arms and Interventions

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.

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

Primary Outcome Measures

Combination of maximum Sequential Organ Failure Assessment (SOFA) Score and death [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 [30 days]
will be hierarchically tested after enrollment of 798 patients

Secondary Outcome Measures

Mean and area under the curve of Sequential Organ Failure Assessment (SOFA) Score [30 days]
minimum score is 0, maximum score is 24; higher score indicates poor outcome (death-adjusted)
Rates of non-invasive ventilation [30 days]
high-flow, continuous positive airway pressure therapy
Rates of renal replacement therapies [30 days]
Change of viral burden [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) [30 days]
Number of patients with systolic/diastolic blood pressure > 180/120 mmHg [30 days]
Hospitalisation due to cardiac decompensation [30 days]
with causal relationship to stopping of ACEI/ARB therapy
Rates of mechanical ventilation [30 days]
Rates of clonal hematopoiesis of indeterminate potential (CHIP) [30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University Innsbruck, University Hospital of Internal Medicine III	Innsbruck	Tyrol	Austria	6020
2	Medical University of Graz	Graz		Austria
3	Landeskrankenhaus Hall	Hall In Tirol		Austria
4	Medical University Innsbruck, Intensive Care and Emergency Medicine Department	Innsbruck		Austria
5	Medical University Innsbruck, University Hospital of Internal Medicine II	Innsbruck		Austria
6	Medical University Innsbruck, University Hospital of Internal Medicine IV	Innsbruck		Austria
7	Medical University Innsbruck, University Hospital of Internal Medicine I	Innsbruck		Austria
8	Medical University Innsbruck, University Hospital of Internal Medicine V	Innsbruck		Austria
9	Klinikum Klagenfurt	Klagenfurt		Austria
10	Bezirkskrankenhaus Kufstein	Kufstein		Austria
11	Klinikum Lienz	Lienz		Austria
12	Bezirkskrankenhaus St. Johann	Sankt Johann In Tirol		Austria
13	Bezirkskrankenhaus Schwaz	Schwaz		Austria
14	Krankenhaus St. Vinzenz Zams	Zams		Austria
15	LMU Klinikum, Medizinische Klinik I	Munich	Bavaria	Germany	81377
16	University Hospital Aachen	Aachen		Germany
17	University Hospital Augsburg	Augsburg		Germany
18	Asklepios Stadtklinik Bad Tölz	Bad Tölz		Germany
19	Klinikum Dachau	Dachau		Germany
20	University Hospital Erlangen	Erlangen		Germany
21	University Hospital Essen	Essen		Germany
22	University of Freiburg	Freiburg		Germany
23	Klinikum Memmingen	Memmingen		Germany
24	LMU Klinikum, Medizinische Klinik III	Munich		Germany
25	LMU Klinikum, Medizinische Klinik II	Munich		Germany
26	LMU Klinikum, Medizinische Klinik IV	Munich		Germany
27	München Klinik Bogenhausen und Schwabing	Munich		Germany
28	Rotkreuzklinikum Munich	Munich		Germany
29	Krankenhaus Mühldorf	Mühldorf		Germany
30	Klinikum Rosenheim	Rosenheim		Germany
31	Krankenhaus Weiden	Weiden		Germany