Clinical trial NCT04312009: Losartan for Patients With COVID-19 Requiring Hospitalization
Official title: Randomized Controlled Trial of Losartan for Patients With COVID-19 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
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2020-03-17
Enrollment: 205
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 requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.


Eligibility criteria: 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

Primary outcomes:
measure: Difference in Estimated (PEEP Adjusted) P/F Ratio at 7 Days
timeFrame: 7 days
Secondary outcomes:
measure: Daily Hypotensive Episodes
timeFrame: 10 days
measure: Proportion of Participants Requiring Vasopressors for Hypotension
timeFrame: 10 days
measure: Proportion of Participants Experiencing Acute Kidney Injury
timeFrame: 10 days
measure: Oxygen Saturation / Fractional Inhaled Oxygen (S/F)
timeFrame: 7 days
measure: 28-Day Mortality
timeFrame: 28 days
measure: 90-Day Mortality
timeFrame: 90 days
measure: ICU Admission
timeFrame: 10 days
measure: Number of Ventilator-Free Days
timeFrame: 28 days
measure: Number of Therapeutic Oxygen-Free Days
timeFrame: 28 days
measure: Number of Vasopressor-Free Days
timeFrame: 10 days
measure: Length of Hospital Stay
timeFrame: 90 days
measure: Disease Severity Rating
timeFrame: 28 days
measure: Change in Viral Load by Nasopharyngeal Swab Day 15
timeFrame: 15 days
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida Health Gainesville
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Burnsville
country: United States
facility: M Health Fairview Ridges Hospital
state: Minnesota
city: Edina
country: United States
facility: M Health Fairview Southdale Hospital
state: Minnesota
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: Robbinsdale
country: United States
facility: North Memorial Health Hospital
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
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, Ingraham NE, Merck LH, Driver BE, Wacker DA, Black LP, Jones AE, Fletcher CV, South AM, Murray TA, Lewandowski C, Farhat J, Benoit JL, Biros MH, Cherabuddi K, Chipman JG, Schacker TW, Guirgis FW, Voelker HT, Koopmeiners JS, Tignanelli CJ; Angiotensin Receptor Blocker Based Lung Protective Strategies for Inpatients With COVID-19 (ALPS-IP) Investigators. Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e222735. doi: 10.1001/jamanetworkopen.2022.2735.
citation: Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.