Clinical trial NCT04311177: Losartan for Patients With COVID-19 Not Requiring Hospitalization
Official title: Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Corona Virus Infection
Acute Respiratory Distress Syndrome
SARS-CoV Infection
Keywords: COVID-19
Corona Virus
SARS-COV-2
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2020-03-17
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Percentage of Participants Admitted to the Hospital
timeFrame: 15 days
Secondary outcomes:
measure: Change in PROMIS Dyspnea Scale
timeFrame: 10 days
measure: Change in SF-12 Physical Composite Score
timeFrame: 10 days
measure: Change in SF-12 Mental Composite Score
timeFrame: 10 days
measure: Daily Maximum Temperature
timeFrame: 10 days
measure: Count of Participants With an Emergency Department or Clinic Presentation
timeFrame: 28 days
measure: Disease Severity Rating Day 15
timeFrame: 15 days
measure: Change in Viral Load by Nasopharyngeal Swab at Day 9
timeFrame: 9 days
measure: Change in Viral Load by Nasopharyngeal Swab at Day 15
timeFrame: 15 days
measure: Percentage of Patients Admitted to the Intensive Care Unit Within 15 Days
timeFrame: 15 days
measure: Need for Oxygen Therapy at 15 Days
timeFrame: 15 days
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: M Health Fairview University of Minnesota Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Health System
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Christopher Tignanelli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Michael Puskarich, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.