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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.
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, 34 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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| External Control | No Intervention | Matched - contemporaneous control who met enrollment criteria and were treated at UKHS during the COVID-19 pandemic period. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Losartan | Drug | 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 14 days of losartan treatment |
| Number of Participants With Mechanical Ventilation Use |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias Salathe | University of Kansas Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32658300 | Derived | Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish. |
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Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)
Beginning 3 months and ending 5 years following article publication
Proposals should be directed to msalathe@kumc.edu. To gain access, data requestors will need to sign a data access agreement.
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External control group were hospitalized during study period and met enrollment criteria and were not enrolled. Participants were matched to losartan group on baseline characteristics.
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| ID | Title | Description |
|---|---|---|
| FG000 | Open Label Losartan | 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion |
| FG001 | External Control | A group of external controls matched to the enrolled participants |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Open Label Losartan | 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 14 days of losartan treatment |
|
From enrollment to hospital discharge, up to day 14.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open Label Losartan | 34 patients with COVID-19 and respiratory failure participated in the study and were placed on losartan 25 mg once daily on study day 0. Losartan dose was increased to 50 mg once daily on study day 3. Participants continued losartan until they experienced resolution of respiratory failure (normal oxygen levels on room air), were discharged from the hospital, met stoppage criteria or completed 14 days of therapy. Losartan: 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Low hemoglobin | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Matthias Salathe | Kansas University Medical Center | 9135886000 | msalathe@kumc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 29, 2020 | Oct 27, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 1, 2020 | Oct 27, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D012131 | Respiratory Insufficiency |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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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.
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Number of participants with mechanical ventilation use
| 14 days of losartan treatment |
| Days on Mechanical Ventilation | 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 | 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 | Days on non-invasive positive pressure ventilation or high flow nasal cannula | 14 days of losartan treatment |
| Number of Participants With Transfer to ICU From Non-ICU Hospital Bed | Number of participants with transfer to ICU from non-ICU hospital bed | 14 days of losartan treatment |
| ICU Length of Stay (Days) | ICU length of stay (days) | 14 days of losartan treatment |
| in Hospital Mortality Rate | in hospital mortality rate | 14 days after study enrollment |
| Hospital Length of Stay (Days) | Hospital length of stay (days) | from enrollment through hospital discharge |
| Cumulative Number of Participants With of Severe Adverse Events | Cumulative number of participants with severe adverse events | 14 days of losartan treatment |
| Number of Participants With Increase of Supplemental Oxygen Needs From Baseline. | Number of participants with increase in supplemental oxygen needs from baseline. | 14 days of losartan treatment |
| Number of Participants With Medications With Possible Antiviral Activity (Hydroxychloroquine, Lopinavir/Ritonavir, Ribavirin or Remdesivir) or Adjunctive Therapy Use (e.g., Tocilizumab) | Number of participants with medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab) | 14 days of losartan treatment |
| Number of Participants With Extracorporeal Membrane Oxygenation Use | Number of participants with extracorporeal membrane oxygenation use | 14 days of losartan treatment |
| Number of Participants With Renal Replacement Therapy Use | Number of participants with renal replacement therapy use | 14 days of losartan treatment |
| Number of Participants With Intolerance to High Dose (50mg) Losartan After Tolerating 25mg | Number of participants with intolerance to high dose (50mg) losartan after tolerating 25mg | 14 days of losartan treatment |
| BG001 | External Controls | 46 external controls matched to losartan participants upon baseline characteristics. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | External Controls | 46 external controls matched to losartan participants upon baseline characteristics. |
|
|
| Secondary | 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 | Posted | Median | Inter-Quartile Range | days | 14 days of losartan treatment |
|
|
|
| Secondary | Number of Participants With Mechanical Ventilation Use | Number of participants with mechanical ventilation use | Posted | Count of Participants | Participants | 14 days of losartan treatment |
|
|
|
| Secondary | Days on Mechanical Ventilation | Days on mechanical ventilation | Posted | Median | Inter-Quartile Range | days | 14 days of losartan treatment |
|
|
|
| Secondary | Number of Participants With Non-invasive Positive Pressure Ventilation or Heated High Flow Nasal Cannula Use | Number of participants with non-invasive positive pressure ventilation or heated high flow nasal cannula use | Posted | Count of Participants | Participants | 14 days of losartan treatment |
|
|
|
| Secondary | Days on Non-invasive Positive Pressure Ventilation or High Flow Nasal Cannula | Days on non-invasive positive pressure ventilation or high flow nasal cannula | Posted | Median | Inter-Quartile Range | days | 14 days of losartan treatment |
|
|
|
| Secondary | Number of Participants With Transfer to ICU From Non-ICU Hospital Bed | Number of participants with transfer to ICU from non-ICU hospital bed | Data regarding transfer to ICU was not collected for any participants during study period and thus not reported. | Posted | 14 days of losartan treatment |
|
|
| Secondary | ICU Length of Stay (Days) | ICU length of stay (days) | Posted | Median | Inter-Quartile Range | days | 14 days of losartan treatment |
|
|
|
| Secondary | in Hospital Mortality Rate | in hospital mortality rate | Posted | Count of Participants | Participants | 14 days after study enrollment |
|
|
|
| Secondary | Hospital Length of Stay (Days) | Hospital length of stay (days) | Posted | Median | Inter-Quartile Range | days | from enrollment through hospital discharge |
|
|
|
| Secondary | Cumulative Number of Participants With of Severe Adverse Events | Cumulative number of participants with severe adverse events | Posted | Number | participants | 14 days of losartan treatment |
|
|
|
| Secondary | Number of Participants With Increase of Supplemental Oxygen Needs From Baseline. | Number of participants with increase in supplemental oxygen needs from baseline. | Posted | Count of Participants | Participants | 14 days of losartan treatment |
|
|
|
| Secondary | Number of Participants With Medications With Possible Antiviral Activity (Hydroxychloroquine, Lopinavir/Ritonavir, Ribavirin or Remdesivir) or Adjunctive Therapy Use (e.g., Tocilizumab) | Number of participants with medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab) | Posted | Count of Participants | Participants | 14 days of losartan treatment |
|
|
|
| Secondary | Number of Participants With Extracorporeal Membrane Oxygenation Use | Number of participants with extracorporeal membrane oxygenation use | Posted | Count of Participants | Participants | 14 days of losartan treatment |
|
|
|
| Secondary | Number of Participants With Renal Replacement Therapy Use | Number of participants with renal replacement therapy use | This outcome was not collected for study participants, thus results are not reported | Posted | 14 days of losartan treatment |
|
|
| Secondary | Number of Participants With Intolerance to High Dose (50mg) Losartan After Tolerating 25mg | Number of participants with intolerance to high dose (50mg) losartan after tolerating 25mg | Posted | Count of Participants | Participants | 14 days of losartan treatment |
|
|
|
| 1 |
| 30 |
| 0 |
| 30 |
| 24 |
| 30 |
| EG001 | External Controls | 46 external controls matched to losartan participants upon baseline characteristics. | 3 | 46 | 0 | 46 | 44 | 46 |
| Elevated AST | Hepatobiliary disorders | MedDRA 10.0 | Systematic Assessment |
|
| Elevated ALT | Hepatobiliary disorders | MedDRA 10.0 | Systematic Assessment |
|
| Elevated creatinine | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
|
| hypotension | Vascular disorders | MedDRA 10.0 | Systematic Assessment |
|
| Elevated Alkaline phosphatase | Hepatobiliary disorders | MedDRA 10.0 | Systematic Assessment |
|
| Elevated potassium | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Low platelets | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |