Study of Open Label Losartan in COVID-19

NCT04335123 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: STUDY00145514
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19. Briefly, 34 patients with COVID-19 and respiratory failure who meet eligibility criteria and agree to participation in the study will be placed on losartan 25 mg daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria (detailed below) or complete 14 days of therapy. Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group. We will also collect medical information relating to safety criteria on historical controls treated at the University of Kansas Hospital in the 30 days prior to the study start date and during the study period.

Conditions

COVID-19

Keywords

COVID-19; losartan; respiratory failure; SARS-CoV-2

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events as Assessed by Protocol Definition of AE

  Safety will be reported based on Protocol defined AEs. For the purpose of this protocol, an AE will be defined as as any untoward medical occurrence in a subject during the study listed under DMSB - Anticipated Adverse Events and Grading Scale section of this protocol as well as safety monitoring data listed on protocol table 1 as well as stoppage criteria for losartan. The event does not necessarily have a causal relationship with the treatment. AEs will be collected for both study groups, treatment and control from the time the ICF is signed until the subject completes study participation.

  14 days of losartan treatment

Secondary Outcomes (15)

• Number of Days on Supplemental Oxygen in Respiratory Failure Due to COVID-19

  14 days of losartan treatment

• Number of Participants With Mechanical Ventilation Use

  14 days of losartan treatment

• Days on Mechanical Ventilation

  14 days of losartan treatment

• Number of Participants With Non-invasive Positive Pressure Ventilation or Heated High Flow Nasal Cannula Use

  14 days of losartan treatment

• Days on Non-invasive Positive Pressure Ventilation or High Flow Nasal Cannula

  14 days of losartan treatment

Study Arms (2)

Open Label Losartan

EXPERIMENTAL

50 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg once daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria or complete 14 days of therapy.

Drug: Losartan

External Control

NO INTERVENTION

Matched - contemporaneous control who met enrollment criteria and were treated at UKHS during the COVID-19 pandemic period.

Interventions

Losartan DRUG

25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion

Also known as: Cozaar

Open Label Losartan

Eligibility Criteria

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

You may qualify if:

• Age \>18 years admitted to the University of Kansas Health System.
• Confirmation of infection with SARS-CoV-2 by PCR testing.
• Hypoxic respiratory failure Requiring mechanical ventilation or oxygen OR a SpO2 ≤94% on room air or a PaO2/FiO2 (P/F) ratio \<300 OR tachypnea (respiratory rate ≥24 breaths/min). Criteria to be met within 48 hours prior to Day 0.
• Other concomitant medications such as antivirals and hydroxychloroquine are allowed.
• Participants prescribed standard of care (SOC) losartan (25mg QD) within 48 hours of consenting may be considered for enrollment if eligibility criteria are met based on EMR data assessment, i.e. no other ARB or ACE prior to SOC medication administration. If participant is eligible and signs consent form, investigational losartan 25mg QD will be ordered to replace SOC prescription on the following scheduled dose.

You may not qualify if:

• Pregnancy.
• Respiratory failure due to a process other than COVID-19.
• Intolerance to ARBs.
• Current chronic use of medication with known interactions with losartan including NSAIDs (intermittent prior use is acceptable), potassium supplementation aliskiren.
• Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic recorded on at least two readings 30 min apart.
• Need for vasopressors, unless norepinephrine ≤0.1 µg/kg/min
• Hyperkalemia (serum K+ \>5.5 mM).
• Known cardiac failure (left ventricular ejection fraction ≤35%), renal insufficiency (Cockcroft-Gault \<30 mL/min/1.73 m2 or urinary output \<20 mL/h), hepatic failure (LFTs \> 5x normal upper limit).
• Known renal artery stenosis.
• Neurological, psychiatric, endocrine or neoplastic diseases that are judged to interfere with participation in the study.
• On another interventional trial (including one for COVID-19) that excludes participation.

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Related Publications (1)

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

  PMID: 32658300 DERIVED

MeSH Terms

Conditions

COVID-19; Respiratory Insufficiency

Interventions

Losartan

Condition Hierarchy (Ancestors)

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

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: Dr Matthias Salathe
• Organization: Kansas University Medical Center

msalathe@kumc.edu

9135886000

Study Officials

• Matthias Salathe

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor- University of Kansas Medical Center

Model Details: 30 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg once daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group. We will also collect medical information relating to safety criteria on historical controls treated at the University of Kansas Hospital in the 30 days prior to the study start date and during the study period.

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 6, 2020
• Study Start: April 4, 2020
• Primary Completion: June 21, 2020
• Study Completion: August 17, 2020
• Last Updated: August 2, 2024
• Results First Posted: August 2, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Proposals should be directed to msalathe@kumc.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)