Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Losartan for Patients With COVID-19 Not Requiring Hospitalization

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04311177
Recruitment Status : Recruiting
First Posted : March 17, 2020
Last Update Posted : June 16, 2020
Sponsor:
Collaborator:
The Minnesota Foundation
Information provided by (Responsible Party):
University of Minnesota

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).

Condition or disease Intervention/treatment Phase
Corona Virus Infection Acute Respiratory Distress Syndrome SARS-CoV Infection Drug: Losartan Other: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 580 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization
Actual Study Start Date : April 9, 2020
Estimated Primary Completion Date : April 1, 2021
Estimated Study Completion Date : April 1, 2021


Arm Intervention/treatment
Experimental: Losartan
Participants in this arm will receive the study drug, Losartan.
Drug: Losartan
Losartan; 25 mg daily; oral administration
Other Name: Cozaar

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




Primary Outcome Measures :
  1. Hospital Admission [ Time Frame: 15 days ]

    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.



Secondary Outcome Measures :
  1. Change in PROMIS Dyspnea Functional Limitations [ Time Frame: baseline, 10 days ]

    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.


  2. Change in PROMIS Dyspnea Severity [ Time Frame: baseline, 10 days ]

    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.


  3. Daily Maximum Temperature [ Time Frame: 10 days ]
    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.

  4. Emergency Department/Clinic Presentations [ Time Frame: 28 days ]
    Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.

  5. Disease Severity Rating Day 7 [ Time Frame: 7 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.

  6. Disease Severity Rating Day 15 [ Time Frame: 15 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.

  7. Disease Severity Rating Day 28 [ Time Frame: 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.

  8. Viral Load by Oropharyngeal Swab Day 9 [ Time Frame: 9 days ]
    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.

  9. Viral Load by Oropharyngeal Swab Day 15 [ Time Frame: 15 days ]
    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.

  10. Ventilator-Free Days [ Time Frame: 28 days ]
    Outcome reported as the mean number of days participants in each arm did not require ventilator use.

  11. Therapeutic Oxygen-Free Days [ Time Frame: 28 days ]
    Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.

  12. Need for Hospital Admission at 15 Days [ Time Frame: 15 days ]
    Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.

  13. Need for Oxygen Therapy at 15 Days [ Time Frame: 15 days ]
    Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04311177


Contacts
Layout table for location contacts
Contact: Christopher Tignanelli, MD 612-624-4373 Covid19trial@umn.edu
Contact: Michael Puskarich, MD, MS 612-624-4373 Covid19trial@umn.edu

Locations
Layout table for location information
United States, Minnesota
Hennepin County Medical Center Recruiting
Minneapolis, Minnesota, United States, 55415
M Health Fairview University of Minnesota Medical Center Recruiting
Minneapolis, Minnesota, United States, 55455
Sub-Investigator: Jeffrey Chipman, MD         
Sub-Investigator: Ron Reikoff, MD         
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Sub-Investigator: Timothy Schacker, MD         
Sub-Investigator: Nicholas Ingraham, MD         
Sub-Investigator: David Wacker, MD         
Sub-Investigator: Michelle Biros, MD, MS         
Mayo Clinic Health System Recruiting
Rochester, Minnesota, United States, 55415
Sponsors and Collaborators
University of Minnesota
The Minnesota Foundation
Investigators
Layout table for investigator information
Principal Investigator: Christopher Tignanelli, MD University of Minnesota
Principal Investigator: Michael Puskarich, MD, MS University of Minnesota
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT04311177    
Other Study ID Numbers: SURG-2020-28683
First Posted: March 17, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Keywords provided by University of Minnesota:
COVID-19
Corona Virus
SARS-COV-2
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Coronavirus Infections
Severe Acute Respiratory Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Virus Diseases
Lung Injury
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Respiratory Tract Infections
Losartan
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action