Condition category
Infections and Infestations
Date applied
22/06/2020
Date assigned
10/07/2020
Last edited
07/08/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 February 2021

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

Trial website

Contact information

Type

Public

Primary contact

Dr Gustaf Edgren

ORCID ID

http://orcid.org/0000-0002-2198-4745

Contact details

Sjukhusbacken 10
Stockholm
11867
Sweden
+46 86164782
gustaf.edgren@ki.se

Type

Scientific

Additional contact

Dr Anders Hedman

ORCID ID

Contact details

VO Kardiologi
Södersjukhuset AB
Stockholm
118 83
Sweden
+46-8-616 100 00
anders.hedman@sll.se

Additional identifiers

EudraCT number

2020-002040-22

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

RAAS blockagE in SARS COV-2 Critically ill patiEnts– a Randomized controlled trial

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

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

Study design

Open-label pragmatic phase IV randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

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

Phase

Phase IV

Drug names

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 trial start date

21/04/2020

Overall trial end date

28/02/2021

Reason abandoned (if study stopped)

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

750

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

01/02/2021

Locations

Countries of recruitment

Sweden

Trial participating centre

Södersjukhuset
Sjukhusbacken 10
Stockholm
11867
Sweden

Sponsor information

Organisation

Stockholm South General Hospital

Sponsor details

VO Kardiologi
Sjukhusbacken 10
Stockholm
11867
Sweden
+46 86161000
info@sodersjukhuset.se

Sponsor type

Hospital/treatment centre

Website

https://www.sodersjukhuset.se/

Funders

Funder type

Government

Funder name

Vetenskapsrådet

Alternative name(s)

Swedish Research Council

Funding Body Type

unknown

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in peer-reviewed journal.

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date.

Intention to publish date

01/05/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.