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

Trial Profile

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

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 05 Jun 2020

At a glance

  • Drugs Losartan (Primary)
  • Indications COVID 2019 infections
  • Focus Therapeutic Use
  • Most Recent Events

    • 15 Apr 2020 Status changed from not yet recruiting to recruiting.
    • 01 Apr 2020 Planned initiation date changed from 16 Mar 2020 to 2 Apr 2020.
    • 19 Mar 2020 New trial record

Trial Overview

Purpose

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.

Primary Endpoints

Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days

description: 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.
time_frame: 7 days

Other Endpoints

Daily Hypotensive Episodes

description: 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.
time_frame: 10 days

Hypotension Requiring Vasopressors

description: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
time_frame: 10 days

Acute Kidney Injury

description: 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.
time_frame: 10 days

Sequential Organ Failure Assessment (SOFA) Total Score

description: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.
time_frame: 10 days

Oxygen Saturation / Fractional Inhaled Oxygen (F/S)

description: 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 F/S ratio is unitless.
time_frame: 10 days

28-Day Mortality

description: Outcome reported as the number of participants who have expired at 28 days post enrollment.
time_frame: 28 days

90-Day Mortality

description: Outcome reported as the number of participants who have expired at 90 days post enrollment.
time_frame: 90 days

ICU Admission

description: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
time_frame: 10 days

Number of Ventilator-Free Days

description: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
time_frame: 10 days

Number of Therapeutic Oxygen-Free Days

description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
time_frame: 10 days

Number of Vasopressor-Free Days

description: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
time_frame: 10 days

Length of ICU Stay

description: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
time_frame: 10 days

Length of Hospital Stay

description: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
time_frame: 10 days

Incidence of Respiratory Failure

description: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.
time_frame: 10 days

Change in PROMIS Dyspnea Functional Limitations

description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea.
In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.
time_frame: 10 days

Change in PROMIS Dyspnea Severity

description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea.
The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.
time_frame: 10 days

Disease Severity Rating

description: 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.
time_frame: 10 days

Viral Load by Nasopharyngeal Swab Day 9

description: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
time_frame: 9 days

Viral Load by Nasopharyngeal Swab Day 15

description: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
time_frame: 15 days

Viral Load by Blood Day 9

description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
time_frame: 9 days

Viral Load by Blood Day 15

description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
time_frame: 15 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 200

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

- Presumptive positive laboratory test for Covid-19 based on local laboratory standard - Admission to the hospital with a respiratory Sequential Organ Failure Assessment (SOFA) score ≥1 and increased oxygen requirement compared to baseline among those on home O2 - Randomization within 24 hours of presentation of hospital admission or within 24 hours of a positive test result, whichever is later

Patient Exclusion Criteria

- Randomization > 24 hours of admission order - 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 - Pregnancy 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 patients of child bearing potential 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 III or 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

Trial Details

Identifiers

Identifier Owner
NCT04312009 ClinicalTrials.gov: US National Institutes of Health
SURG2020-28675 -
INV017069 -

Trial Dates

  • Initiation Dates

    Planned : 02 Apr 2020

    Actual : 13 Apr 2020

  • Primary Completion Dates

    Planned : 01 Apr 2021

  • End Dates

    Planned : 01 Apr 2021

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase II
  • Location USA
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
LosartanPrimary Drug Oral Tablet

Losartan

Participants in this arm will receive the study drug, Losartan. Drug: Losartan (Losartan; 50 mg daily; oral administration) Other Name: Cozaar

Placebo

Participants in this arm will receive a placebo treatment. Other: Placebo (Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Christopher Tignanelli, MD
612-625-7911
ctignane@umn.edu
show details
University of Minnesota USA
David Wacker, MD University of Minnesota USA
Jeffrey Chipman, MD M Health Fairview University of Minnesota Medical Center USA
Lisa Merck, MD, MPH University of Florida Gainesviile USA
Michael Puskarich, MD, MS
612-626-6911
mike-em@umn.edu
show details
University of Minnesota USA
Michelle Biros, MD, MS University of Minnesota USA
Nicholas Ingraham, MD University of Minnesota USA
Ron Reikoff, MD M Health Fairview University of Minnesota Medical Center USA
Timothy Schacker, MD University of Minnesota USA

Centres

Centre Name Location Trial Centre Country
Bill and Melinda Gates Foundation
-
-
Hennepin County Medical Center Minneapolis, Minnesota USA
M Health Fairview University of Minnesota Medical Center Minneapolis, Minnesota USA
University of Florida Gainesviile Gainesville, Florida USA
University of Minnesota
-
-
University of Minnesota Minneapolis, Minnesota USA

Trial History

Event Date Event Type Comment
05 Jun 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 05 Jun 2020
15 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 17 Apr 2020
01 Apr 2020 Other trial event Planned initiation date changed from 16 Mar 2020 to 2 Apr 2020. Updated 06 Apr 2020
19 Mar 2020 New trial record New trial record Updated 19 Mar 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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