Using the blood pressure medication losartan to improve outcomes for patients with SARS CoV-2
| ISRCTN | ISRCTN48734830 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN48734830 |
| EudraCT/CTIS number | 2020-002040-22 |
- Submission date
- 22/06/2020
- Registration date
- 10/07/2020
- Last edited
- 13/12/2021
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
There is an ongoing pandemic of severe respiratory disease (Covid-19) caused by a novel Coronavirus (SARS-CoV-2) that was first detected in China in December, 2019. The first cases were observed in Sweden in January, 2020, and there is currently ongoing spread in all Swedish regions. Unfortunately, there is currently no available specific treatment for Covid-19. Several investigators have suggested that treatment with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) might lead to an improvement in disease outcomes for Covid-19 patients.
Who can participate?
Patients treated in a hospital in Sweden for confirmed Covid-19
What does the study involve?
Participating patients will be randomized to either receive a blood pressure-lowering drug (losartan) in addition to standard treatment, or standard treatment alone. Patients will be followed up for 28 days
What are the possible benefits and risks of participating?
The risks with losartan treatment are well-known and involve having too-low blood pressure, kidney problems and salt balance problems. All participating patients will be monitored for these problems and they will be dealt with if they occur. Possible benefits may involve a less severe course of the Covid-19 disease.
Where is the study run from?
The hospital Södersjukhuset in Stockholm, Sweden
When is the study starting and how long is it expected to run for?
April 2020 to January 2022
Who is funding the study?
Swedish Research Council
Who is the main contact?
Dr Anders Hedman (scientific), anders.hedman@sll.se
Dr Gustaf Edgran (public), gustaf.edgren@ki.se
Contact information
Public
Sjukhusbacken 10
Stockholm
11867
Sweden
 ORCID ID |
0000-0002-2198-4745 |
|---|---|
| Phone | +46 86164782 |
| gustaf.edgren@ki.se |
Scientific
VO Kardiologi
Södersjukhuset AB
Stockholm
118 83
Sweden
| Phone | +46-8-616 100 00 |
|---|---|
| anders.hedman@sll.se |
Study information
| Study design | Open-label pragmatic phase IV randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | RAAS blockagE in SARS COV-2 Critically ill patiEnts– a Randomized controlled trial |
| Study acronym | RECOVER |
| Study hypothesis | The study will test the hypothesis that addition of losartan to standard treatment will decrease risk of the occurrence of the composite endpoint of admission to intensive care unit, or death |
| Ethics approval(s) | Approved 18/05/2020, Swedish Ethical Review Authority (Etikprövningsmyndigheten, Box 2110, 750 02, Uppsala, Sweden; +46 10-475 08 00; registrator@etikprovning.se), ref: 2020-02185 |
| Condition | COVID-19 (SARS-CoV-2 infection) |
| Intervention | Patients in the active arm of the trial will be receiving open-label Losartan in a dosage titrated with regards to blood pressure and renal function up to a maximum of 100 mg once daily. Active treatment with Losartan will continue until death or discharge from hospital, or for a maximum of 28 days post-randomization. The starting dose will be 25 mg for patients with a systolic blood pressure of 120 - 130 mmHg at randomization and 50 mg for patients with a systolic blood pressure of > 140 mmHg. Patients randomized to the control group will receive standard treatment. There will be no placebo intervention. If blood pressure medication is warranted according to existing guidelines a non-ACEi or ARB medication should be chosen. The randomization will be performed using an online randomization system, in a 1:1 ratio, with a pre-generated random sequence in blocks of random size from 2 to 6. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Losartan |
| Primary outcome measure | Time to first occurrence of a composite endpoint (admission to intensive care unit, or death), within 28 days of randomization |
| Secondary outcome measures | Measured using case report form: 1. All-cause mortality at day 28 from randomization 2. Occurrence of ICU admission during hospital stay 3. Need for and duration of invasive mechanical ventilation 4. Peak level and area under the curve during hospitalization for National Early Warning score 2 (NEWS2) score 5. Peak level and area under the curve during hospitalization for CRP score |
| Overall study start date | 21/04/2020 |
| Overall study end date | 31/01/2022 |
| Reason abandoned (if study stopped) | Participant recruitment issue |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 750 |
| Total final enrolment | 302 |
| Participant inclusion criteria | 1. Positive PCR laboratory test for SARS-CoV-2 2. Age > 18 years 3. Admitted for in-hospital care no more than 48 hours earlier 4. GCS ≥ 14 |
| Participant exclusion criteria | 1. Admitted to ICU prior to randomization. 2. Current treatment with blood pressure lowering agent, affecting the RAAS system (i.e. Angiotensin Converting Enzyme inhibitor (ACEi), Angiotensin Receptor Blocker (ARB), Aldosteron antagonist or Renin inhibitor) 3. Patients with heart condition eg. heart failure with reduced ejection fraction, EF < 40%, who has an evidence based indication for ACE inhibitors or Angiotensin receptor blockers 4. Prior serious adverse reaction to an ARB or ACEi 5. Systolic blood pressure below 120 mmHg or symptomatic hypotension. Blood pressure will be taken in supine position after 5 minutes rest with manual or automatic blood pressure manometers 6. Estimated Glomerular Filtration Rate (eGFR) of < 50ml/min/1.73 m² 7. Potassium > 5 mEq/l 8. Women of childbearing age. Pregnant or breastfeeding. Women that are postmenopausal can be included. Women and childbearing age can be included after a negative pregnancy test 9. Known renal artery stenosis 10. Severe hepatic failure (i.e. ALAT/ASAT > 5x normal upper limit) 11. Volume depletion, chock or new onset of acute kidney injury that, in the opinion of the investigator, would preclude administration of ARB/ACE-inhibitors 12. Any condition or therapy which would make the participant unsuitable for the study, according to the investigators opinion 13. Inability to provide informed consent 14. Moribund or palliative patients deemed unlike to survive hospital stay or who cannot make an informed decision for participations (e.g. non-adults or patients with dementia) |
| Recruitment start date | 03/08/2020 |
| Recruitment end date | 31/12/2021 |
Locations
Countries of recruitment
- Sweden
Study participating centre
Stockholm
11867
Sweden
Sponsor information
Hospital/treatment centre
VO Kardiologi
Sjukhusbacken 10
Stockholm
11867
Sweden
| Phone | +46 86161000 |
|---|---|
| info@sodersjukhuset.se | |
| Website | https://www.sodersjukhuset.se/ |
"ROR" |
https://ror.org/00ncfk576 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Swedish Research Council, VR
- Location
- Sweden
Results and Publications
| Intention to publish date | 01/05/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in peer-reviewed journal. |
| IPD sharing plan | Data will likely not be made publicly available due to data privacy issues |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version v5 | 22/06/2020 | 07/08/2020 | No | No |
Additional files
- ISRCTN48734830_Protocol_v5_22Jun2020.pdf
- uploaded 07/08/2020
Editorial Notes
13/12/2021: The study has been halted at the first interim analysis due to futility on account of a lower than expected event rate. Total final enrolment and Individual participant data (IPD) sharing statement added.
16/02/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/02/2021 to 31/12/2021.
2. The overall trial end date was changed from 28/02/2021 to 31/01/2022.
3. The intention to publish date was changed from 01/05/2021 to 01/05/2022.
07/08/2020: Uploaded protocol (not peer reviewed) Version 5 22 June 2020.
10/07/2020: Internal review.
09/07/2020: Trial’s existence confirmed by Swedish Medical Products Agency.
