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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: Recruiting
Phase of Trial: Phase II

Latest Information Update: 17 Jun 2020

At a glance

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

    • 09 Apr 2020 Planned number of patients changed from 516 to 580.
    • 09 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.

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 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: baseline, 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: baseline, 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 2019 infections treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 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

  • 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; 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
17 Jun 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 17 Jun 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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