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Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization

Trial Profile

Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization

Status: Completed
Phase of Trial: Phase II

Latest Information Update: 16 Feb 2021

At a glance

  • Drugs Losartan (Primary)
  • Indications COVID-19 respiratory infection
  • Focus Therapeutic Use
  • Most Recent Events

    • 12 Feb 2021 Status changed from active, no longer recruiting to completed.
    • 13 Nov 2020 Status changed from recruiting to active, no longer recruiting.
    • 09 Apr 2020 Planned number of patients changed from 516 to 580.

Trial Overview

Purpose

This is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).

Primary Endpoints

Hospital Admission

description: Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization.
Currently, there is a pre-planned pooled analysis with a national trial network under development.
time_frame: 15 days

Other Endpoints

Change in PROMIS Dyspnea scale

description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported shortness of breath in general, intensity, frequency and duration on a 0-10 scale, with 0 being no symptoms and 10 being the most severe. Finally, the patient answers the question "I've been short of breath" using a 0-4 scale, 0 being none and the most severe. There is no validated, unified single score and each item is evaluated individually.
time_frame: 10 days

Change in SF-12 Physical Composite Score

description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Physical score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. 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

Change in SF-12 Mental Composite Score

description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Mental composite score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
time_frame: 10 days

Daily Maximum Temperature

description: Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.
time_frame: 10 days

Emergency Department/Clinic Presentations

description: Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
time_frame: 28 days

Disease Severity Rating Day 7

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: 7 days

Disease Severity Rating Day 15

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: 15 days

Disease Severity Rating Day 28

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: 28 days

Viral Load by Oropharyngeal Swab Day 9

description: Participants will collect oropharyngeal swabs 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 Oropharyngeal Swab Day 15

description: Participants will collect oropharyngeal swabs 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

Ventilator-Free Days

description: Outcome reported as the mean number of days participants in each arm did not require ventilator use.
time_frame: 28 days

Therapeutic Oxygen-Free Days

description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.
time_frame: 28 days

Need for Hospital Admission at 15 Days

description: Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.
time_frame: 15 days

Need for Oxygen Therapy at 15 Days

description: Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.
time_frame: 15 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID-19 respiratory infection treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 580

    Actual: 580

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

Patient Inclusion Criteria

- Positive laboratory test for COVID-19 based on local laboratory standard - Age greater than or equal to 18 years of age - One of the following: Upper respiratory symptoms (cough, rhinorrhea) or fever (>101.5) or loss of taste / smell

Patient Exclusion Criteria

- Randomization > 72 hours of meeting inclusion criteria - Randomization > 7 days of symptom onset - 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 women - Females able to have children 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, condom use or abstinence during the study. All participants of child bearing potential enrolled in this fashion will be informed of the teratogenic risks. - 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 (must be have been measured within 1 month of enrollment) 4. Other kidney disease that in the opinion of the investigator, would affect losartan clearance - Patient reported dehydration and significantly decreased urine output in the past 72 hours - Most recent systolic blood pressure prior to enrollment <110 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. Other liver disease that in the opinion of the investigator, would affect losartan clearance 4. Documented AST or ALT > 3 times the upper limit of normal within 3 months of randomization (if available in electronic medical record) - Potassium >5.0 mmol/L (must have been measured within 1 month) of enrollment - Concurrent treatment with aliskiren - Inability to obtain informed consent - Enrollment in another blinded randomized clinical trial for COVID

Trial Details

Identifiers

Identifier Owner
NCT04311177 ClinicalTrials.gov: US National Institutes of Health
SURG2020-28683 -

Trial Dates

  • Initiation Dates

    Planned : 02 Apr 2020

    Actual : 09 Apr 2020

  • Primary Completion Dates

    Planned : 01 Apr 2021

    Actual : 01 Feb 2021

  • End Dates

    Planned : 01 Apr 2021

    Actual : 01 Feb 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; 25 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
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
Hennepin County Medical Center Minneapolis, Minnesota USA
M Health Fairview University of Minnesota Medical Center Minneapolis, Minnesota USA
Mayo Clinic Health System Rochester, Minnesota USA
The Minnesota Foundation
-
-
University of Minnesota
-
-
University of Minnesota Minneapolis, Minnesota USA

Trial History

Event Date Event Type Comment
16 Feb 2021 Other trial event Last checked against ClinicalTrials.gov record. Updated 16 Feb 2021
12 Feb 2021 Status change - completed Status changed from active, no longer recruiting to completed. Updated 16 Feb 2021
13 Nov 2020 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting. Updated 18 Nov 2020
09 Apr 2020 Other trial event Planned number of patients changed from 516 to 580. Updated 14 Apr 2020
09 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 14 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 Other trial event Planned number of patients changed from 478 to 516. Updated 26 Mar 2020
18 Mar 2020 New trial record New trial record Updated 18 Mar 2020

References

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

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