Losartan for Patients With COVID-19 Not Requiring Hospitalization

• ClinicalTrials.gov Identifier: NCT04311177
• Recruitment Status: Completed
• First Posted: March 17, 2020
• Results First Posted: May 4, 2022
• Last Update Posted: May 4, 2022
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Tracking Information

• First Submitted Date: March 13, 2020
• First Posted Date: March 17, 2020
• Results First Submitted Date: March 16, 2022
• Results First Posted Date: May 4, 2022
• Last Update Posted Date: May 4, 2022
• Actual Study Start Date: April 9, 2020
• Actual Primary Completion Date: February 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 28, 2022)

Percentage of Participants Admitted to the Hospital [ Time Frame: 15 days ]

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.

Original Primary Outcome Measures (submitted: March 13, 2020)

Hospital Admission [ Time Frame: 28 days ]

Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease.

Current Secondary Outcome Measures (submitted: April 28, 2022)

• Change in PROMIS Dyspnea Scale [ Time Frame: 10 days ]
  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 [ Time Frame: 10 days ]
  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 [ Time Frame: 10 days ]
  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 [ 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.
• Count of Participants With an Emergency Department or Clinic Presentation [ Time Frame: 28 days ]
  Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
• 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.
• Change in Viral Load by Nasopharyngeal Swab at Day 9 [ Time Frame: 9 days ]
  Viral load is measured as number of viral genetic copies per mL.
• Change in Viral Load by Nasopharyngeal Swab at Day 15 [ Time Frame: 15 days ]
  Viral load is measured as number of viral genetic copies per mL.
• Percentage of Patients Admitted to the Intensive Care Unit Within 15 Days [ Time Frame: 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 [ Time Frame: 15 days ]
  Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.

Original Secondary Outcome Measures (submitted: March 13, 2020)

• 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.
• 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.
• Fever Incidence Day 3 [ Time Frame: 10 days ]
  Participants will record oral temperature every day for 10 days. Outcome is reported as body temperature (in degrees Celsius) at day 3.
• Fever Incidence Day 5 [ Time Frame: 10 days ]
  Participants will record oral temperature every day for 10 days. Outcome is reported as body temperature (in degrees Celsius) at day 5.
• Fever Incidence Day 7 [ Time Frame: 10 days ]
  Participants will record oral temperature every day for 10 days. Outcome is reported as body temperature (in degrees Celsius) at day 7.
• Fever Incidence Day 10 [ Time Frame: 10 days ]
  Participants will record oral temperature every day for 10 days. Outcome is reported as body temperature (in degrees Celsius) at day 10.
• Severity of Symptoms upon Hospital Admission [ Time Frame: 28 days ]
  Outcome is reported as the number of participants in each arm who are admitted to inpatient hospital care and who present with organ failure (as determined by physician) at the time of admission.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Losartan
  Losartan; 25 mg daily; oral administration
  Other Name: Cozaar
• Other: Placebo
  Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration

Study Arms

• Experimental: Losartan
  Participants in this arm will receive the study drug, Losartan.
  Intervention: Drug: Losartan
• Placebo Comparator: Placebo
  Participants in this arm will receive a placebo treatment.
  Intervention: Other: Placebo

Publications *

• 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.
• Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117. pii: 20110. Swedish.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 28, 2022): 117
• Original Estimated Enrollment (submitted: March 13, 2020): 478
• Actual Study Completion Date: February 1, 2021
• Actual Primary Completion Date: February 1, 2021 (Final data collection date for primary outcome measure)

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:

  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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04311177
• Other Study ID Numbers: SURG-2020-28683
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Minnesota
• Study Sponsor: University of Minnesota
• Collaborators: Not Provided

Investigators

• Principal Investigator: Christopher Tignanelli, MD; University of Minnesota
• Principal Investigator: Michael Puskarich, MD, MS; University of Minnesota

• PRS Account: University of Minnesota
• Verification Date: May 2022