Corona Virus InfectionPhase 2NCT04312009
Losartan for Patients With COVID-19 Requiring Hospitalization
A Phase 2 study testing Losartan in people with Corona Virus Infection and Acute Respiratory Distress Syndrome, run by University of Minnesota at 13 sites in United States.
Trial summary
This is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corona Virus Infection, Acute Respiratory Distress Syndrome, SARS-CoV Infection
- What is being tested?
- Losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 205 participants
- Where
- 13 sitesUnited States
- Study dates
- 13 Apr 2020to 1 Feb 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presumptive positive laboratory test for Covid-19 based on local laboratory standard
- Age greater than or equal to 18 years of age
- Admission to the hospital with a respiratory SOFA >=1 and increased oxygen requirement compared to baseline among those on home O2
- Randomization within 48 hours of presentation of hospital admission or within 48 hours of a positive test result, whichever is later
Who cannot join
- Randomization > 48 hours of admission order or positive test result, whichever is later
- Currently taking an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB)
- Prior reaction or intolerance to an ARB or ACE inhibitor, including but not limited to angioedema
- Pregnant or breastfeeding
- Lack of negative urine or serum pregnancy test
- Not currently taking a protocol allowed version of contraception: intrauterine device, Depo-formulation of hormonal contraception (e.g. medroxyprogesterone acetate / Depo-Provera), subcutaneous contraceptive (e.g. Nexplanon), daily oral contraceptives with verbalized commitment to taking daily throughout the study period; use of condoms or agree to abstain from sexual intercourse during the study. All women of child bearing age enrolled in this fashion will be informed of the teratogenic risks. If enrolled under LAR, they will be informed of the risks after regaining capacity.
Show all 20Show fewer
- Patient reported history or electronic medical record history of kidney disease, defined as:
- Any history of dialysis
- History of chronic kidney disease stage IV
- Estimated Glomerular Filtration Rate (eGFR) of < 30ml/min/1.73 m2 at the time of randomization
- Severe dehydration at the time of enrollment in the opinion of the investigator or bedside clinician
- Most recent mean arterial blood pressure prior to enrollment <65 mmHg
- Patient reported history or electronic medical record history of severe liver disease, defined as:
- Cirrhosis
- History of hepatitis B or C
- Documented AST or ALT > 3 times the upper limit of normal measured within 24 hours prior to randomization
- Potassium >5.0 within 24 hours prior to randomization unless a repeat value was <=5.0
- Treatment with aliskiren
- Inability to obtain informed consent from participant or legally authorized representative
- Enrollment in another blinded randomized clinical trial for COVID
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Grady Memorial Hospital
Atlanta, Georgia, 30303
M Health Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Cooper University Hospital
Camden, New Jersey, 08103
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
Henry Ford Hospital
Detroit, Michigan, 48202
M Health Fairview Southdale Hospital
Edina, Minnesota, 55435
University of Florida Health Gainesville
Gainesville, Florida, 32611
University of Mississippi Medical Center
Jackson, Mississippi, 39216
University of Florida Health Jacksonville
Jacksonville, Florida, 32209
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
M Health Fairview University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
University of Minnesota
Minneapolis, Minnesota, 55455
North Memorial Health Hospital
Robbinsdale, Minnesota, 55422
About this study
Official title: Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization
This is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
- Being tested
- Losartan, Placebo
- Keywords
- COVID-19, Corona Virus, SARS-COV-2
- Medical subject headings
- Coronavirus Infections, Respiratory Distress Syndrome, Severe Acute Respiratory Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Cozaar
Losartan; 50 mg daily; oral administration
PlaceboOther
Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Experimental | Participants in this arm will receive the study drug, Losartan. Receives: Drug: Losartan |
| Placebo | Placebo comparator | Participants in this arm will receive a placebo treatment. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days
Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.
Measured: 7 days
Secondary outcomes (13)
Daily Hypotensive Episodes
Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.
Measured: 10 days
Proportion of Participants Requiring Vasopressors for Hypotension
Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Measured: 10 days
Proportion of Participants Experiencing Acute Kidney Injury
Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines:
Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.
Measured: 10 days
Oxygen Saturation / Fractional Inhaled Oxygen (S/F)
Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The S/F ratio is unitless.
Measured: 7 days
28-Day Mortality
Outcome reported as the number of participants who have expired at 28 days post enrollment.
Measured: 28 days
90-Day Mortality
Outcome reported as the number of participants who have expired at 90 days post enrollment.
Measured: 90 days
ICU Admission
Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Measured: 10 days
Number of Ventilator-Free Days
Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Measured: 28 days
Number of Therapeutic Oxygen-Free Days
Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
Measured: 28 days
Number of Vasopressor-Free Days
Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Measured: 10 days
Length of Hospital Stay
Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
Measured: 90 days
Disease Severity Rating
Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measured: 28 days
Change in Viral Load by Nasopharyngeal Swab Day 15
Nasopharyngeal swabs will be collected at baseline and day 15. Viral load is measured as number of viral genetic copies per mL.
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2020
- Study start13 Apr 2020
- Primary completion1 Feb 2021
- Study completion1 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Corona Virus InfectionStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 205 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Christopher Tignanelli, MD, Principal investigator, University of MinnesotaMichael Puskarich, MD, MS, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04312009
- Sponsor's protocol ID
- SURG-2020-28675
- Other IDs
- INV-017069
- Status last verified
- Jun 2022
- First submitted
- 13 Mar 2020
- Last updated
- 29 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Puskarich MA, Ingraham NE, Merck LH, Driver BE, Wacker DA, Black LP, Jones AE, Fletcher CV, South AM, Murray TA, Lewandowski C, Farhat J, Benoit JL, Biros MH, Cherabuddi K, Chipman JG, Schacker TW, Guirgis FW, Voelker HT, Koopmeiners JS, Tignanelli CJ; Angiotensin Receptor Blocker Based Lung Protective Strategies for Inpatients With COVID-19 (ALPS-IP) Investigators. Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e222735. doi: 10.1001/jamanetworkopen.2022.2735.
PubMed 35294537Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.
PubMed 32658300
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization
- ClinicalTrials.gov ID
- NCT04312009
- Acronym / sponsor ID
- SURG-2020-28675
- Keywords
- COVID-19, Corona Virus, SARS-COV-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 205 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Study start
- 13 Apr 2020 (actual)
- Primary completion
- 1 Feb 2021 (actual)
- Study completion
- 1 Feb 2021 (actual)
- First posted
- 17 Mar 2020 (actual)
- Results
- Posted 29 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Losartan | Experimental | Drug: LosartanParticipants in this arm will receive the study drug, Losartan. |
| Placebo | Placebo comparator | Other: PlaceboParticipants in this arm will receive a placebo treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Presumptive positive laboratory test for Covid-19 based on local laboratory standard
- Age greater than or equal to 18 years of age
- Admission to the hospital with a respiratory SOFA >=1 and increased oxygen requirement compared to baseline among those on home O2
- Randomization within 48 hours of presentation of hospital admission or within 48 hours of a positive test result, whichever is later
Key exclusion criteria (20 listed)
- Randomization > 48 hours of admission order or positive test result, whichever is later
- Currently taking an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB)
- Prior reaction or intolerance to an ARB or ACE inhibitor, including but not limited to angioedema
- Pregnant or breastfeeding
- Lack of negative urine or serum pregnancy test
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LosartanAlso: CozaarLosartan; 50 mg daily; oral administration | Drug | Losartan |
| PlaceboPlacebo (microcrystalline methylcellulose, gelatin capsule); oral administration | Other | Placebo |
Primary outcome
Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days
Time frame: 7 days
Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.
13 secondary outcomes
Daily Hypotensive Episodes
Time frame: 10 days
Proportion of Participants Requiring Vasopressors for Hypotension
Time frame: 10 days
Proportion of Participants Experiencing Acute Kidney Injury
Time frame: 10 days
Oxygen Saturation / Fractional Inhaled Oxygen (S/F)
Time frame: 7 days
28-Day Mortality
Time frame: 28 days
90-Day Mortality
Time frame: 90 days
ICU Admission
Time frame: 10 days
Number of Ventilator-Free Days
Time frame: 28 days
Number of Therapeutic Oxygen-Free Days
Time frame: 28 days
Number of Vasopressor-Free Days
Time frame: 10 days
Length of Hospital Stay
Time frame: 90 days
Disease Severity Rating
Time frame: 28 days
Change in Viral Load by Nasopharyngeal Swab Day 15
Time frame: 15 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35294537Puskarich MA, Ingraham NE, Merck LH, Driver BE, Wacker DA, Black LP, Jones AE, Fletcher CV, South AM, Murray TA, Lewandowski C, Farhat J, Benoit JL, Biros MH, Cherabuddi K, Chipman JG, Schacker TW, Guirgis FW, Voelker HT, Koopmeiners JS, Tignanelli CJ; Angiotensin Receptor Blocker Based Lung Protective Strategies for Inpatients With COVID-19 (ALPS-IP) Investigators. Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e222735. doi: 10.1001/jamanetworkopen.2022.2735.
- Derived from this study: PubMed 32658300Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Tignanelli, MD principal investigator
University of Minnesota
Michael Puskarich, MD, MS principal investigator
University of Minnesota
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Losartan in people with Corona Virus Infection and Acute Respiratory Distress Syndrome, run by University of Minnesota at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04312009, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2022.