Trial Outcomes & Findings for Stopping ACE-inhibitors in COVID-19 (NCT NCT04353596)
NCT ID: NCT04353596
Last Updated: 2022-09-13
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
216 participants
Primary outcome timeframe
30 days
Results posted on
2022-09-13
Participant Flow
Between April 20, 2020, and Jan 20, 2021, 204 participants were randomly assigned to discontinuation (n=109) or continuation (n=107) of RAS inhibition, at 35 centres, including 19 university clinics and 16 large referral hospitals, in Austria and Germany.
Of 2301 patients, who were assessed for eligibility, 216 underwent randomization. 1921 were excluded due violation of inclusion or exclusion criteria.
Participant milestones
| Measure |
Discontinuation Group
Discontinuation of chronic ACEI or ARB pretreatment
|
Continuation Group
Continuation of chronic ACEI or ARB pretreatment
|
|---|---|---|
|
Overall Study
STARTED
|
109
|
107
|
|
Overall Study
Per Protocol
|
104
|
100
|
|
Overall Study
COMPLETED
|
104
|
100
|
|
Overall Study
NOT COMPLETED
|
5
|
7
|
Reasons for withdrawal
| Measure |
Discontinuation Group
Discontinuation of chronic ACEI or ARB pretreatment
|
Continuation Group
Continuation of chronic ACEI or ARB pretreatment
|
|---|---|---|
|
Overall Study
Protocol Violation
|
4
|
4
|
|
Overall Study
no evidence of recent SARS-CoV-2
|
1
|
3
|
Baseline Characteristics
Stopping ACE-inhibitors in COVID-19
Baseline characteristics by cohort
| Measure |
Discontinuation Group
n=104 Participants
Chronic pretreatment with ACEI or ARB will be stopped or replaced.
Substitution with an alternative substance class was at the discretion of the treating physician
|
Continuation Group
n=100 Participants
No intervention, which means further treatment with ACEI or ARB. In patients, randomized to continuation, it may be needed to stop ACEI or ARB (e.g. hypotension with beginning sepsis) irrespective of the study.
|
Total
n=204 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74 years
n=99 Participants
|
75 years
n=107 Participants
|
75 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=99 Participants
|
36 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
65 Participants
n=99 Participants
|
64 Participants
n=107 Participants
|
129 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
104 Participants
n=99 Participants
|
100 Participants
n=107 Participants
|
204 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
Austria
|
59 participants
n=99 Participants
|
57 participants
n=107 Participants
|
116 participants
n=206 Participants
|
|
Region of Enrollment
Germany
|
45 participants
n=99 Participants
|
43 participants
n=107 Participants
|
88 participants
n=206 Participants
|
|
BMI
|
28 "kg per m^2"
n=99 Participants
|
27.4 "kg per m^2"
n=107 Participants
|
27.6 "kg per m^2"
n=206 Participants
|
|
Hypertension
|
100 Participants
n=99 Participants
|
99 Participants
n=107 Participants
|
199 Participants
n=206 Participants
|
|
Current Smoker
|
6 Participants
n=99 Participants
|
99 Participants
n=107 Participants
|
105 Participants
n=206 Participants
|
|
Dyslipidaemia
|
38 Participants
n=99 Participants
|
48 Participants
n=107 Participants
|
86 Participants
n=206 Participants
|
|
Diabetes
|
30 Participants
n=99 Participants
|
37 Participants
n=107 Participants
|
67 Participants
n=206 Participants
|
|
Coronary artery disease
|
22 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
|
Heart failure
|
12 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Chronic obstructive pulmonary disease
|
10 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
|
Atrial fibrillation
|
18 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Malignant disease
|
7 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Kidney disease
|
16 Participants
n=99 Participants
|
21 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
|
History of stroke
|
8 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Angiotensin-converting enzyme inhibitor
|
57 Participants
n=99 Participants
|
58 Participants
n=107 Participants
|
115 Participants
n=206 Participants
|
|
Angiotensin II receptor blocker
|
47 Participants
n=99 Participants
|
42 Participants
n=107 Participants
|
89 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 30 daysThe 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).
Outcome measures
| Measure |
Discontinuation Group
n=104 Participants
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 Participants
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Composite of the Maximum Sequential Organ Failure Assessment (SOFA) Score and Death Within 30 Days
|
0 score on a scale
Interval 0.0 to 2.0
|
1 score on a scale
Interval 0.0 to 3.0
|
PRIMARY outcome
Timeframe: 30 daysComposite of admission to ICU, mechanical ventilation, and death
Outcome measures
| Measure |
Discontinuation Group
n=104 Participants
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 Participants
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Composite of Admission to an Intensive Care Unit (ICU), the Use of Mechanical Ventilation, or All-cause Death
|
21 Participants
|
26 Participants
|
SECONDARY outcome
Timeframe: 30 daysminimum score is 0, maximum score is 24; higher score indicates poor outcome (death-adjusted)
Outcome measures
| Measure |
Discontinuation Group
n=104 Participants
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 Participants
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Mean of Sequential Organ Failure Assessment (SOFA) Score
|
0 score on a scale
Interval 0.0 to 0.31
|
0.12 score on a scale
Interval 0.0 to 0.78
|
SECONDARY outcome
Timeframe: 30 daysNumber of Participants with Non-invasive Ventilation
Outcome measures
| Measure |
Discontinuation Group
n=104 Participants
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 Participants
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Rates of Non-invasive Ventilation
|
19 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: 30 daysOutcome measures
| Measure |
Discontinuation Group
n=104 Participants
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 Participants
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Rates of Renal Replacement Therapies
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 30 daysOutcome measures
| Measure |
Discontinuation Group
n=104 Participants
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 Participants
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Number of Patients With Systolic/Diastolic Blood Pressure > 180/120 mmHg
|
7 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: 30 dayswith causal relationship to stopping of ACEI/ARB therapy
Outcome measures
| Measure |
Discontinuation Group
n=104 Participants
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 Participants
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Hospitalisation Due to Cardiac Decompensation
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 30 daysOutcome measures
| Measure |
Discontinuation Group
n=104 Participants
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 Participants
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Rates of Mechanical Ventilation
|
10 Participants
|
8 Participants
|
Adverse Events
Discontinuation Group
Serious events: 25 serious events
Other events: 13 other events
Deaths: 8 deaths
Continuation Group
Serious events: 28 serious events
Other events: 7 other events
Deaths: 12 deaths
Serious adverse events
| Measure |
Discontinuation Group
n=104 participants at risk
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 participants at risk
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Worsening of respiratory function
|
20.2%
21/104 • 30 days
|
24.0%
24/100 • 30 days
|
|
Cardiac disorders
Ischemic events
|
0.00%
0/104 • 30 days
|
2.0%
2/100 • 30 days
|
|
Renal and urinary disorders
Urinary tract infection
|
0.96%
1/104 • 30 days
|
0.00%
0/100 • 30 days
|
|
Cardiac disorders
Ventricular tachycardia
|
0.96%
1/104 • 30 days
|
0.00%
0/100 • 30 days
|
|
Infections and infestations
Worsening of general condition
|
1.9%
2/104 • 30 days
|
2.0%
2/100 • 30 days
|
Other adverse events
| Measure |
Discontinuation Group
n=104 participants at risk
Discontinuation of ACEI or ARB therapy
|
Continuation Group
n=100 participants at risk
Continuation of ACEI or ARB therapy
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Worsening of respiratory function
|
4.8%
5/104 • 30 days
|
2.0%
2/100 • 30 days
|
|
Renal and urinary disorders
Urinary tract infection
|
1.9%
2/104 • 30 days
|
0.00%
0/100 • 30 days
|
|
Renal and urinary disorders
Elevation of creatinine
|
0.00%
0/104 • 30 days
|
1.0%
1/100 • 30 days
|
|
Vascular disorders
Hypertension
|
1.9%
2/104 • 30 days
|
2.0%
2/100 • 30 days
|
|
Infections and infestations
Worsening of general condition
|
3.8%
4/104 • 30 days
|
2.0%
2/100 • 30 days
|
Additional Information
Prof. Dr. Axel Bauer
Medizinische Universität Innsbruck/ Medical University Innsbruck
Phone: 0043 512 504 25621
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place