Back to resultsStudy of Open Label Losartan in COVID-19
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Losartan
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, losartan, respiratory failure, SARS-CoV-2
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Pregnancy.
- Respiratory failure due to a process other than COVID-19.
- Intolerance to ARBs.
- Previous treatment with an ARB or ACE inhibitor (see exception in inclusion criteria).
- 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.
Sites / Locations
- University of Kansas Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open Label Losartan
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of days on supplemental oxygen in respiratory failure due to COVID-19
Number of days on supplemental oxygen in respiratory failure due to COVID-19
Incidence of mechanical ventilation use
Incidence of mechanical ventilation use
Days on mechanical ventilation
Days on mechanical ventilation
Incidence of non-invasive positive pressure ventilation or heated high flow nasal cannula use
Incidence of non-invasive positive pressure ventilation or heated high flow nasal cannula use
Days on non-invasive positive pressure ventilation or high flow nasal cannula
Days on non-invasive positive pressure ventilation or high flow nasal cannula
Incidence of transfer to ICU from non-ICU hospital bed
Incidence of transfer to ICU from non-ICU hospital bed
ICU length of stay (days)
ICU length of stay (days)
30-day mortality rate
30-day mortality rate
Hospital length of stay (days)
Hospital length of stay (days)
Cumulative incidence of severe adverse events
Cumulative incidence of severe adverse events
Cumulative incidence of adverse events
Cumulative incidence of adverse events
Change from baseline in oxygenation
Change from baseline in oxygenation
Incidence of medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab)
Incidence of medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab)
Incidence (and length in days) of extracorporeal membrane oxygenation use
Incidence (and length in days) of extracorporeal membrane oxygenation use
Incidence (and length in days) of renal replacement therapy use
Incidence (and length in days) of renal replacement therapy use
Intolerance of high dose (50mg) losartan after tolerating 25mg
Intolerance of high dose (50mg) losartan after tolerating 25mg
Full Information
NCT ID
NCT04335123
First Posted
March 31, 2020
Last Updated
May 6, 2021
Sponsor
University of Kansas Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04335123
Brief Title
Study of Open Label Losartan in COVID-19
Official Title
An Open Label Phase 1 Trial of Losartan for Worsening Respiratory Illness in COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
April 4, 2020 (Actual)
Primary Completion Date
June 21, 2020 (Actual)
Study Completion Date
August 17, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Kansas Medical Center
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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, 50 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 (3/25/2020) and during the study period.
Detailed Description
This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19.
Clinical Trial setup:
Detailed inclusion and exclusion criteria are listed below. Briefly, 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 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.
Stoppage criteria for losartan
Hyperkalemia (persistent values >5.5 mM recorded on at least 2 readings).
Worsening renal function (Cockcroft-Gault <30 mL/min/1.73 m2) or urinary output <20 mL/h.
Skin rashes, palpitations or other moderate or severe adverse events (interference with usual daily activities) without clear explanation should warrant immediate cessation of treatment and notification of study personnel.
Development of sustained hypotension defined as SBP <90 mmHg, DBP <60 mmHg recorded on at least two readings 30 min apart or use of norepinephrine >0.1 µg/kg/min.
Any change in monitor lab parameters deemed significant and potentially related to study drug by the Investigator.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19, losartan, respiratory failure, SARS-CoV-2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
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. 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 (3/25/2020) and during the study period.
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open Label Losartan
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Losartan
Other Intervention Name(s)
Cozaar
Intervention Description
25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by protocol definition of AE
Description
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.
Time Frame
14 days of losartan treatment
Secondary Outcome Measure Information:
Title
Number of days on supplemental oxygen in respiratory failure due to COVID-19
Description
Number of days on supplemental oxygen in respiratory failure due to COVID-19
Time Frame
14 days of losartan treatment
Title
Incidence of mechanical ventilation use
Description
Incidence of mechanical ventilation use
Time Frame
14 days of losartan treatment
Title
Days on mechanical ventilation
Description
Days on mechanical ventilation
Time Frame
14 days of losartan treatment
Title
Incidence of non-invasive positive pressure ventilation or heated high flow nasal cannula use
Description
Incidence of non-invasive positive pressure ventilation or heated high flow nasal cannula use
Time Frame
14 days of losartan treatment
Title
Days on non-invasive positive pressure ventilation or high flow nasal cannula
Description
Days on non-invasive positive pressure ventilation or high flow nasal cannula
Time Frame
14 days of losartan treatment
Title
Incidence of transfer to ICU from non-ICU hospital bed
Description
Incidence of transfer to ICU from non-ICU hospital bed
Time Frame
14 days of losartan treatment
Title
ICU length of stay (days)
Description
ICU length of stay (days)
Time Frame
14 days of losartan treatment
Title
30-day mortality rate
Description
30-day mortality rate
Time Frame
30 days after diagnosis of COVID-19
Title
Hospital length of stay (days)
Description
Hospital length of stay (days)
Time Frame
14 days of losartan treatment
Title
Cumulative incidence of severe adverse events
Description
Cumulative incidence of severe adverse events
Time Frame
14 days of losartan treatment
Title
Cumulative incidence of adverse events
Description
Cumulative incidence of adverse events
Time Frame
14 days of losartan treatment
Title
Change from baseline in oxygenation
Description
Change from baseline in oxygenation
Time Frame
14 days of losartan treatment
Title
Incidence of medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab)
Description
Incidence of medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab)
Time Frame
14 days of losartan treatment
Title
Incidence (and length in days) of extracorporeal membrane oxygenation use
Description
Incidence (and length in days) of extracorporeal membrane oxygenation use
Time Frame
14 days of losartan treatment
Title
Incidence (and length in days) of renal replacement therapy use
Description
Incidence (and length in days) of renal replacement therapy use
Time Frame
14 days of losartan treatment
Title
Intolerance of high dose (50mg) losartan after tolerating 25mg
Description
Intolerance of high dose (50mg) losartan after tolerating 25mg
Time Frame
14 days of losartan treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
Pregnancy.
Respiratory failure due to a process other than COVID-19.
Intolerance to ARBs.
Previous treatment with an ARB or ACE inhibitor (see exception in inclusion criteria).
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthias Salathe
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)
IPD Sharing Time Frame
Beginning 3 months and ending 5 years following article publication
IPD Sharing Access Criteria
Proposals should be directed to msalathe@kumc.edu. To gain access, data requestors will need to sign a data access agreement.
Citations:
PubMed Identifier
32658300
Citation
Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.
Results Reference
derived
Learn more about this trial
Study of Open Label Losartan in COVID-19
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