Losartan for Patients With COVID-19 Requiring Hospitalization

Acute Respiratory Distress Syndrome Clinical Trial

Official title:

Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04312009
• Other study ID #: SURG-2020-28675
• Secondary ID: INV-017069
• Status: Completed
• Phase: Phase 2
• Start date: April 13, 2020
• Est. completion date: February 1, 2021

Study information

• Verified date: June 2022
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: February 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

• Patient reported history or electronic medical record history of kidney disease, defined as:

1. Any history of dialysis

2. History of chronic kidney disease stage IV

3. 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:

1. Cirrhosis

2. History of hepatitis B or C

3. 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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Communicable Diseases
• Corona Virus Infection
• Coronavirus Infections
• COVID-19
• Infections
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• SARS-CoV Infection

Intervention

Drug:
• Losartan
Losartan; 50 mg daily; oral administration

Other:
• Placebo
Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration

Locations

Country	Name	City	State
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	M Health Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper University Hospital	Camden	New Jersey
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	M Health Fairview Southdale Hospital	Edina	Minnesota
United States	University of Florida Health Gainesville	Gainesville	Florida
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Florida Health Jacksonville	Jacksonville	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	M Health Fairview University of Minnesota Medical Center	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	North Memorial Health Hospital	Robbinsdale	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota	Bill and Melinda Gates Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	7 days
Secondary	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.	10 days
Secondary	Proportion of Participants Requiring Vasopressors for Hypotension	Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.	10 days
Secondary	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.	10 days
Secondary	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.	7 days
Secondary	28-Day Mortality	Outcome reported as the number of participants who have expired at 28 days post enrollment.	28 days
Secondary	90-Day Mortality	Outcome reported as the number of participants who have expired at 90 days post enrollment.	90 days
Secondary	ICU Admission	Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).	10 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	10 days
Secondary	Length of Hospital Stay	Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.	90 days
Secondary	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.	28 days
Secondary	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.	15 days