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Losartan for Patients With COVID-19 Not Requiring Hospitalization

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ClinicalTrials.gov Identifier: NCT04311177
Recruitment Status : Completed
First Posted : March 17, 2020
Last Update Posted : September 24, 2021
Sponsor:
Collaborator:
The Minnesota Foundation
Information provided by (Responsible Party):
University of Minnesota

Tracking Information
First Submitted Date  ICMJE March 13, 2020
First Posted Date  ICMJE March 17, 2020
Last Update Posted Date September 24, 2021
Actual Study Start Date  ICMJE April 9, 2020
Actual Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2020)
  • Change in PROMIS Dyspnea scale [ Time Frame: 10 days ]
    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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Ventilator-Free Days [ Time Frame: 28 days ]
    Outcome reported as the mean number of days participants in each arm did not require ventilator use.
  • 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.
  • 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.
  • 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  ICMJE
 (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  ICMJE Losartan for Patients With COVID-19 Not Requiring Hospitalization
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Corona Virus Infection
  • Acute Respiratory Distress Syndrome
  • SARS-CoV Infection
Intervention  ICMJE
  • Drug: Losartan
    Losartan; 25 mg daily; oral administration
    Other Name: Cozaar
  • Other: Placebo
    Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Study Arms  ICMJE
  • 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 *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 16, 2021)
162
Original Estimated Enrollment  ICMJE
 (submitted: March 13, 2020)
478
Actual Study Completion Date  ICMJE February 1, 2021
Actual Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04311177
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party University of Minnesota
Study Sponsor  ICMJE University of Minnesota
Collaborators  ICMJE The Minnesota Foundation
Investigators  ICMJE
Principal Investigator: Christopher Tignanelli, MD University of Minnesota
Principal Investigator: Michael Puskarich, MD, MS University of Minnesota
PRS Account University of Minnesota
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP