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Losartan for Patients With COVID-19 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04312009
Recruitment Status : Completed
First Posted : March 17, 2020
Last Update Posted : August 18, 2021
Sponsor:
Collaborator:
Bill and Melinda Gates 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 August 18, 2021
Actual Study Start Date  ICMJE April 13, 2020
Actual Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days [ Time Frame: 7 days ]
Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.
Original Primary Outcome Measures  ICMJE
 (submitted: March 13, 2020)
Sequential Organ Failure Assessment (SOFA) Respiratory Score [ Time Frame: 28 days ]
The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Outcome is reported as only the respiratory component score. Respiratory scores range from 0-4, with higher scores indicating greater chance of mortality due to respiratory failure.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2021)
  • Daily Hypotensive Episodes [ Time Frame: 10 days ]
    Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.
  • Hypotension Requiring Vasopressors [ Time Frame: 10 days ]
    Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
  • Acute Kidney Injury [ Time Frame: 10 days ]
    Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.
  • Sequential Organ Failure Assessment (SOFA) Total Score [ Time Frame: 10 days ]
    The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.
  • Oxygen Saturation / Fractional Inhaled Oxygen (S/F) [ Time Frame: 10 days ]
    Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The S/F ratio is unitless.
  • 28-Day Mortality [ Time Frame: 28 days ]
    Outcome reported as the number of participants who have expired at 28 days post enrollment.
  • 90-Day Mortality [ Time Frame: 90 days ]
    Outcome reported as the number of participants who have expired at 90 days post enrollment.
  • ICU Admission [ Time Frame: 10 days ]
    Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
  • Number of Ventilator-Free Days [ Time Frame: 10 days ]
    Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
  • Number of Therapeutic Oxygen-Free Days [ Time Frame: 10 days ]
    Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
  • Number of Vasopressor-Free Days [ Time Frame: 10 days ]
    Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
  • Length of ICU Stay [ Time Frame: 10 days ]
    Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
  • Length of Hospital Stay [ Time Frame: 10 days ]
    Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
  • Incidence of Respiratory Failure [ Time Frame: 10 days ]
    Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.
  • 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.
  • 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.
  • Disease Severity Rating [ Time Frame: 10 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 Nasopharyngeal Swab Day 9 [ Time Frame: 9 days ]
    Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
  • Viral Load by Nasopharyngeal Swab Day 15 [ Time Frame: 15 days ]
    Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
  • Viral Load by Blood Day 9 [ Time Frame: 9 days ]
    Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
  • Viral Load by Blood Day 15 [ Time Frame: 15 days ]
    Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2020)
  • 28-Day Mortality [ Time Frame: 28 days ]
    Outcome reported as the number of participants who have expired at 28 days post enrollment.
  • 90-Day Mortality [ Time Frame: 90 days ]
    Outcome reported as the number of participants who have expired at 90 days post enrollment.
  • Respiratory Failure Requiring Mechanical Ventilation [ Time Frame: 7 days ]
    Outcome reported as the number of participants receiving in-patient hospital care requiring mechanical ventilation due to respiratory failure.
  • Number of 28-Day Ventilator-Free Days [ Time Frame: 28 days ]
    Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
  • Length of Hospital Stay [ Time Frame: approximately 28 days ]
    Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
  • ICU Admission [ Time Frame: approximately 28 days ]
    Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
  • ICU Length of Stay [ Time Frame: approximately 28 days ]
    Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
  • Acute Kidney Injury [ Time Frame: approximately 28 days ]
    Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines:
    1. Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR
    2. Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR
    3. Urine output less than 0.5 mL/kg/h for 6 hours.
  • Hypotension Requiring Vasopressors [ Time Frame: approximately 28 days ]
    Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
  • Sequential Organ Failure Assessment (SOFA) Total Score [ Time Frame: approximately 14 days ]
    The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.
  • Severity Assessment [ 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.
  • Incidence of Respiratory Failure [ Time Frame: approximately 28 days ]
    Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.
  • Oxygen Saturation / Fractional Inhaled Oxygen (F/S) [ Time Frame: 72 hours ]
    Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.
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 Requiring Hospitalization
Official Title  ICMJE Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization
Brief Summary This is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
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; 50 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)
205
Original Estimated Enrollment  ICMJE
 (submitted: March 13, 2020)
200
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:

  • Presumptive positive laboratory test for Covid-19 based on local laboratory standard
  • Age greater than or equal to 18 years of age
  • Admission to the hospital with a respiratory SOFA >=1 and increased oxygen requirement compared to baseline among those on home O2
  • Randomization within 48 hours of presentation of hospital admission or within 48 hours of a positive test result, whichever is later

Exclusion Criteria:

  • Randomization > 48 hours of admission order or positive test result, whichever is later
  • 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
  • Lack of negative urine or serum pregnancy test
  • 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 period; use of condoms or agree to abstain from sexual intercourse during the study. All women of child bearing age enrolled in this fashion will be informed of the teratogenic risks. If enrolled under LAR, they will be informed of the risks after regaining capacity.
  • 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 at the time of randomization
  • Severe dehydration at the time of enrollment in the opinion of the investigator or bedside clinician
  • Most recent mean arterial blood pressure prior to enrollment <65 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. Documented AST or ALT > 3 times the upper limit of normal measured within 24 hours prior to randomization
  • Potassium >5.0 within 24 hours prior to randomization unless a repeat value was <=5.0
  • Treatment with aliskiren
  • Inability to obtain informed consent from participant or legally authorized representative
  • 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 NCT04312009
Other Study ID Numbers  ICMJE SURG-2020-28675
INV-017069 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
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 Bill and Melinda Gates 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 August 2021

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