Clinical Trial Results:
Effects of discontinuing renin-angiotensin system inhibitors in patients with and without COVID-19
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Summary
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EudraCT number |
2020-001544-26 |
Trial protocol |
DK |
Global end of trial date |
22 Dec 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Nov 2025
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First version publication date |
09 Nov 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RASCOVID-19
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Center for Clinical Metabolic Research, Gentofte Hospital
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Sponsor organisation address |
Gentofte Hospitalsvej 7, Hellerup, Denmark, 2900
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Public contact |
Filip Krag Knop, Center for Clinical Metabolic Research, Gentofte Hospital, 0045 38674266, filip.krag.knop.01@regionh.dk
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Scientific contact |
Filip Krag Knop, Center for Clinical Metabolic Research, Gentofte Hospital, 0045 38674266, filip.krag.knop.01@regionh.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Dec 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Dec 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Dec 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This randomised clinical trial will compare the effects of continuing and discontinuing treatment with ACE inhibitors or ARBs in hospitalised patients with COVID-19 on the number of days alive and out of hospital within 14 days after randomisation (primary endpoint). Furthermore, in order to understand how continuing and discontinuing treatment with RAS inhibition affect RAS and its components, interferon signatures, T cell exhaustion markers and blood pressure, we will investigate how continuing and discontinuing RAS-inhibiting treatment affect these parameters in both hospitalised patients with COVID-19 and in non-hospitalised individuals treated with ACE inhibitors or ARBs without COVID-19.
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Protection of trial subjects |
The protocol-related procedures are associated with minimal discomfort to the participants.
The participants in group A and group B will either not receive their usual ACE inhibitor or ARB or continue their usual therapy during their admission, depending on assignment group. Discontinuation the ACE/ARB therapy may result in a small temporary increase in blood pressure; however, blood pressure is routinely measured and, thus, closely monitored during their hospital admission. In case of admission period of less than 30 days, the participant will be instructed to contact his/her general practitioner at day 30 for blood pressure measurements and continuation of antihypertension therapy. At discharge, for all participants, the site investigator will also inform the general practitioner (an electronic discharge letter) and at day 30, site investigator will contact each participant to remind of contacting the general practitioner for blood pressure measurement and ensure continuation of antihypertensive therapy in both groups. ACE inhibitors and ARBs can be considered symptomatic treatment in heart failure, and thus, patients with systolic heart failure will not be included in the study. It is currently unclear whether or not discontinuation of RAS-inhibiting therapy will improve or worsen the prognosis of patients with COVID-19; therefore, neither the assignment to the continuation nor the discontinuation group can clearly be labelled disadvantageous for the participant.
The total amount of blood loss will be less than 30 ml at each of the samples; this small amount is not expected to have a clinically relevant impact on the outcome for the participant. Participants will not receive any remuneration for participating in the trial.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
15 May 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 38
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Worldwide total number of subjects |
38
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EEA total number of subjects |
38
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
18
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From 65 to 84 years |
16
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85 years and over |
4
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Recruitment
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Recruitment details |
Participants will be recruited amongst COVID-19 positive patients admitted in a COVID-19 clinic in the Capital Region of Copenhagen. Upon admission of patients treated with ACE inhibitors and ARBs, site investigators with an employment at the COVID-19 clinic in question will screen the admitted patients for eligibility. | |||||||||
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Pre-assignment
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Screening details |
A potential participant will be approached during the first days of hospital admission by the site investigator who will present the trial with verbal and written information regarding the project, and the patient will be invited to participate. The patient will be offered 24 hours for consideration of participation in the trial. | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
38 | |||||||||
Number of subjects completed |
38 | |||||||||
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Period 1
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Period 1 title |
Full period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Continue RASi | |||||||||
Arm description |
Participants contunuing RASi | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
RASi
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
RASi treatment with ACE and ARBs as prescribed prior to the inclusion in the trial.
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Arm title
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Discontinue RASi | |||||||||
Arm description |
Participants discontinuing RASi | |||||||||
Arm type |
discontinuing RASi treatment | |||||||||
Investigational medicinal product name |
N/A
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Not mentioned
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Dosage and administration details |
N/A
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Baseline characteristics reporting groups
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Reporting group title |
Continue RASi
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Reporting group description |
Participants contunuing RASi | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Discontinue RASi
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Reporting group description |
Participants discontinuing RASi | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Covid patients
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Paitents with positive PCR for SARS-CoV-2 RNA
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End points reporting groups
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Reporting group title |
Continue RASi
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Reporting group description |
Participants contunuing RASi | ||
Reporting group title |
Discontinue RASi
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Reporting group description |
Participants discontinuing RASi | ||
Subject analysis set title |
Covid patients
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Paitents with positive PCR for SARS-CoV-2 RNA
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End point title |
The primary endpoint is days alive and out of hospital within 14 days after recruitment | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Number of days alive and out of hospital within 14 days after recruitment
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Statistical analysis title |
Welch Two Sample t-test | |||||||||||||||
Comparison groups |
Continue RASi v Discontinue RASi
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Number of subjects included in analysis |
38
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||
P-value |
< 0.05 | |||||||||||||||
Method |
Welch Two Sample t-test | |||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
From inclusion to 14 days after recruitment
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
GCP units SOP | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
F5
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Reporting groups
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Reporting group title |
Continue RASi
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Reporting group description |
Participants contunuing RASi | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Discontinue RASi
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Reporting group description |
Participants discontinuing RASi | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
