Losartan for Patients With COVID-19 Requiring Hospitalization

NCT04312009 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: SURG-2020-28675INV-017069
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 13

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.

Conditions

Corona Virus Infection; Acute Respiratory Distress Syndrome; SARS-CoV Infection

Keywords

COVID-19; Corona Virus; SARS-COV-2

Outcome Measures

Primary Outcomes (1)

• Difference in Estimated (PEEP Adjusted) P/F Ratio at 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.

  7 days

Secondary Outcomes (13)

• Daily Hypotensive Episodes

  10 days

• Proportion of Participants Requiring Vasopressors for Hypotension

  10 days

• Proportion of Participants Experiencing Acute Kidney Injury

  10 days

• Oxygen Saturation / Fractional Inhaled Oxygen (S/F)

  7 days

• 28-Day Mortality

  28 days

Study Arms (2)

Losartan

EXPERIMENTAL

Participants in this arm will receive the study drug, Losartan.

Drug: Losartan

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive a placebo treatment.

Other: Placebo

Interventions

Losartan DRUG

Losartan; 50 mg daily; oral administration

Also known as: Cozaar

Losartan

Placebo OTHER

Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Any history of dialysis
• History of chronic kidney disease stage IV
• 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:
• Cirrhosis
• History of hepatitis B or C

Sponsors & Collaborators

• University of Minnesota: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (13)

University of Florida Health Gainesville

Gainesville, Florida, 32611, United States

Location

University of Florida Health Jacksonville

Jacksonville, Florida, 32209, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

M Health Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

M Health Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

North Memorial Health Hospital

Robbinsdale, Minnesota, 55422, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Related Publications (2)

• 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.

  PMID: 35294537 DERIVED

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

  PMID: 32658300 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome; COVID-19

Interventions

Losartan

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Christopher Tignanelli
• Organization: University of Minnesota

ctignane@umn.edu

612-626-1968

Study Officials

• Christopher Tignanelli, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Michael Puskarich, MD, MS

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2020
• First Posted: March 17, 2020
• Study Start: April 13, 2020
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: June 29, 2022
• Results First Posted: June 29, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)