search
Back to results

Losartan for Patients With COVID-19 Not Requiring Hospitalization

Primary Purpose

Corona Virus Infection, Acute Respiratory Distress Syndrome, SARS-CoV Infection

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Losartan
Placebo
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corona Virus Infection focused on measuring COVID-19, Corona Virus, SARS-COV-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Sites / Locations

  • Hennepin County Medical Center
  • M Health Fairview University of Minnesota Medical Center
  • University of Minnesota
  • Mayo Clinic Health System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Losartan

Placebo

Arm Description

Participants in this arm will receive the study drug, Losartan.

Participants in this arm will receive a placebo treatment.

Outcomes

Primary Outcome Measures

Percentage of Participants Admitted to the Hospital
Outcome reported as the percentage 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.

Secondary Outcome Measures

Change in PROMIS Dyspnea Scale
The PROMIS dyspnea scale consists of 4 subscales. 3 (1. general shortness of breath, 2. intensity, and 3. Frequency) are scored from 0 (no symptoms) to 10 (most severe). The 4th subscale is scored from 0-4 in response to the question "I've been short of breath" with 0 representing none and 4 the most severe, for a total range of 0-34. Results are difference between enrollment and day 10. There are no units.
Change in SF-12 Physical Composite Score
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.
Change in SF-12 Mental Composite Score
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.
Daily Maximum Temperature
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.
Count of Participants With an Emergency Department or Clinic Presentation
Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
Disease Severity Rating Day 15
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 at Day 9
Viral load is measured as number of viral genetic copies per mL.
Change in Viral Load by Nasopharyngeal Swab at Day 15
Viral load is measured as number of viral genetic copies per mL.
Percentage of Patients Admitted to the Intensive Care Unit Within 15 Days
Outcome reported as the percent of participants in each arm who require ICU admission by day 15 following randomization.
Need for Oxygen Therapy at 15 Days
Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.

Full Information

First Posted
March 13, 2020
Last Updated
May 2, 2022
Sponsor
University of Minnesota
search

1. Study Identification

Unique Protocol Identification Number
NCT04311177
Brief Title
Losartan for Patients With COVID-19 Not Requiring Hospitalization
Official Title
Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
April 9, 2020 (Actual)
Primary Completion Date
February 1, 2021 (Actual)
Study Completion Date
February 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection, Acute Respiratory Distress Syndrome, SARS-CoV Infection
Keywords
COVID-19, Corona Virus, SARS-COV-2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
117 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Losartan
Arm Type
Experimental
Arm Description
Participants in this arm will receive the study drug, Losartan.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants in this arm will receive a placebo treatment.
Intervention Type
Drug
Intervention Name(s)
Losartan
Other Intervention Name(s)
Cozaar
Intervention Description
Losartan; 25 mg daily; oral administration
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Primary Outcome Measure Information:
Title
Percentage of Participants Admitted to the Hospital
Description
Outcome reported as the percentage 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
Secondary Outcome Measure Information:
Title
Change in PROMIS Dyspnea Scale
Description
The PROMIS dyspnea scale consists of 4 subscales. 3 (1. general shortness of breath, 2. intensity, and 3. Frequency) are scored from 0 (no symptoms) to 10 (most severe). The 4th subscale is scored from 0-4 in response to the question "I've been short of breath" with 0 representing none and 4 the most severe, for a total range of 0-34. Results are difference between enrollment and day 10. There are no units.
Time Frame
10 days
Title
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
Title
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
Title
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
Title
Count of Participants With an Emergency Department or Clinic Presentation
Description
Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
Time Frame
28 days
Title
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
Title
Change in Viral Load by Nasopharyngeal Swab at Day 9
Description
Viral load is measured as number of viral genetic copies per mL.
Time Frame
9 days
Title
Change in Viral Load by Nasopharyngeal Swab at Day 15
Description
Viral load is measured as number of viral genetic copies per mL.
Time Frame
15 days
Title
Percentage of Patients Admitted to the Intensive Care Unit Within 15 Days
Description
Outcome reported as the percent of participants in each arm who require ICU admission by day 15 following randomization.
Time Frame
15 days
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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: Any history of dialysis History of chronic kidney disease stage IV Estimated Glomerular Filtration Rate (eGFR) of < 30ml/min/1.73 m2 (must be have been measured within 1 month of enrollment) 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: Cirrhosis History of hepatitis B or C Other liver disease that in the opinion of the investigator, would affect losartan clearance 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Tignanelli, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Puskarich, MD, MS
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
M Health Fairview University of Minnesota Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic Health System
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34195577
Citation
Puskarich MA, Cummins NW, Ingraham NE, Wacker DA, Reilkoff RA, Driver BE, Biros MH, Bellolio F, Chipman JG, Nelson AC, Beckman K, Langlois R, Bold T, Aliota MT, Schacker TW, Voelker HT, Murray TA, Koopmeiners JS, Tignanelli CJ. A multi-center phase II randomized clinical trial of losartan on symptomatic outpatients with COVID-19. EClinicalMedicine. 2021 Jun 17;37:100957. doi: 10.1016/j.eclinm.2021.100957. eCollection 2021 Jul.
Results Reference
result
PubMed Identifier
32658300
Citation
Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.
Results Reference
derived

Learn more about this trial

Losartan for Patients With COVID-19 Not Requiring Hospitalization

We'll reach out to this number within 24 hrs