Losartan for Patients With COVID-19 Requiring Hospitalization

Phase 2

Completed

Conditions: Acute Respiratory Distress Syndrome
SARS-CoV Infection
Corona Virus Infection

Interventions: Other: Placebo
Drug: Losartan

Registration Number: NCT04312009

Lead Sponsor: University of Minnesota

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 205

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants in this arm will receive a placebo treatment.
Losartan	Losartan	Participants in this arm will receive the study drug, Losartan.

Primary Outcome Measures

Name	Time	Method
Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days	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.

Secondary Outcome Measures

Name	Time	Method
Daily Hypotensive Episodes	10 days	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.
Proportion of Participants Requiring Vasopressors for Hypotension	10 days	Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Proportion of Participants Experiencing Acute Kidney Injury	10 days	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.
Oxygen Saturation / Fractional Inhaled Oxygen (S/F)	7 days	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.
90-Day Mortality	90 days	Outcome reported as the number of participants who have expired at 90 days post enrollment.
Number of Therapeutic Oxygen-Free Days	28 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-Day Mortality	28 days	Outcome reported as the number of participants who have expired at 28 days post enrollment.
ICU Admission	10 days	Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Number of Ventilator-Free Days	28 days	Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Number of Vasopressor-Free Days	10 days	Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Length of Hospital Stay	90 days	Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
Disease Severity Rating	28 days	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.
Change in Viral Load by Nasopharyngeal Swab Day 15	15 days	Nasopharyngeal swabs will be collected at baseline and day 15. Viral load is measured as number of viral genetic copies per mL.

Trial Locations

Locations (13): University of Cincinnati Medical Center
🇺🇸
Cincinnati, Ohio, 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
Grady Memorial Hospital
🇺🇸
Atlanta, Georgia, United States
University of Florida Health Jacksonville
🇺🇸
Jacksonville, Florida, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
North Memorial Health Hospital
🇺🇸
Robbinsdale, Minnesota, United States
University of Florida Health Gainesville
🇺🇸
Gainesville, Florida, United States
M Health Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Cooper University Hospital
🇺🇸
Camden, New Jersey, United States
M Health Fairview Southdale Hospital
🇺🇸
Edina, Minnesota, United States

Losartan for Patients With COVID-19 Requiring Hospitalization

Recruitment & Eligibility

Study & Design

Trial Locations

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