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

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).

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 117 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
• Actual Primary Completion Date: February 1, 2021
• Actual Study Completion Date: February 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
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. 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.
8. 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.
9. 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.
10. 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.

Eligibility Criteria

• 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

Contacts and Locations

Locations

United States, Minnesota

Hennepin County Medical Center

Minneapolis, Minnesota, United States, 55415

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, United States, 55455

University of Minnesota

Minneapolis, Minnesota, United States, 55455

Mayo Clinic Health System

Rochester, Minnesota, United States, 55415

Sponsors and Collaborators

University of Minnesota

Investigators

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

  Study Documents (Full-Text)

Documents provided by University of Minnesota:

Study Protocol and Statistical Analysis Plan  [PDF] April 5, 2020

Informed Consent Form  [PDF] April 7, 2020

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04311177
• Other Study ID Numbers: SURG-2020-28683
• First Posted: March 17, 2020
• Results First Posted: May 4, 2022
• Last Update Posted: May 4, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Infections; Communicable Diseases; COVID-19; Coronavirus Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Disease Attributes; Pathologic Processes; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Losartan; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action