COVID-19Phase 1NCT04335123
Study of Open Label Losartan in COVID-19
A Phase 1 study testing Losartan in people with COVID-19, run by University of Kansas Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Losartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2020to 17 Aug 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
Official title: An Open Label Phase 1 Trial of Losartan for Worsening Respiratory Illness in COVID-19
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.
Read the 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, 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
- 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Cozaar
25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Losartan |
| External Control | No intervention | Matched - contemporaneous control who met enrollment criteria and were treated at UKHS during the COVID-19 pandemic period. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 days of losartan treatment
Secondary outcomes (15)
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
Measured: 14 days of losartan treatment
Number of Participants With Mechanical Ventilation Use
Number of participants with mechanical ventilation use
Measured: 14 days of losartan treatment
Days on Mechanical Ventilation
Days on mechanical ventilation
Measured: 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
Measured: 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
Measured: 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
Measured: 14 days of losartan treatment
ICU Length of Stay (Days)
ICU length of stay (days)
Measured: 14 days of losartan treatment
in Hospital Mortality Rate
in hospital mortality rate
Measured: 14 days after study enrollment
Hospital Length of Stay (Days)
Hospital length of stay (days)
Measured: from enrollment through hospital discharge
Cumulative Number of Participants With of Severe Adverse Events
Cumulative number of participants with severe adverse events
Measured: 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.
Measured: 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)
Measured: 14 days of losartan treatment
Number of Participants With Extracorporeal Membrane Oxygenation Use
Number of participants with extracorporeal membrane oxygenation use
Measured: 14 days of losartan treatment
Number of Participants With Renal Replacement Therapy Use
Number of participants with renal replacement therapy use
Measured: 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
Measured: 14 days of losartan treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start4 Apr 2020
- Primary completion21 Jun 2020
- Study completion17 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthias Salathe, MD, University of Kansas Medical Center
- Investigators
- Matthias Salathe, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04335123
- Sponsor's protocol ID
- STUDY00145514
- Status last verified
- Feb 2024
- First submitted
- 31 Mar 2020
- Last updated
- 2 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)
Publications
Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.
PubMed 32658300
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase 1 Trial of Losartan for Worsening Respiratory Illness in COVID-19
- ClinicalTrials.gov ID
- NCT04335123
- Acronym / sponsor ID
- STUDY00145514
- Conditions
- COVID-19
- Keywords
- COVID-19, losartan, respiratory failure, SARS-CoV-2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- 4 Apr 2020 (actual)
- Primary completion
- 21 Jun 2020 (actual)
- Study completion
- 17 Aug 2020 (actual)
- First posted
- 6 Apr 2020 (actual)
- Results
- Posted 2 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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, 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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Open Label Losartan | Experimental | Drug: Losartan50 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LosartanAlso: Cozaar25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion | Drug | Open Label Losartan |
Primary outcome
Number of Participants With Treatment-related Adverse Events as Assessed by Protocol Definition of AE
Time frame: 14 days of losartan treatment
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.
15 secondary outcomes
Number of Days on Supplemental Oxygen in Respiratory Failure Due to COVID-19
Time frame: 14 days of losartan treatment
Number of Participants With Mechanical Ventilation Use
Time frame: 14 days of losartan treatment
Days on Mechanical Ventilation
Time frame: 14 days of losartan treatment
Number of Participants With Non-invasive Positive Pressure Ventilation or Heated High Flow Nasal Cannula Use
Time frame: 14 days of losartan treatment
Days on Non-invasive Positive Pressure Ventilation or High Flow Nasal Cannula
Time frame: 14 days of losartan treatment
Number of Participants With Transfer to ICU From Non-ICU Hospital Bed
Time frame: 14 days of losartan treatment
ICU Length of Stay (Days)
Time frame: 14 days of losartan treatment
in Hospital Mortality Rate
Time frame: 14 days after study enrollment
Hospital Length of Stay (Days)
Time frame: from enrollment through hospital discharge
Cumulative Number of Participants With of Severe Adverse Events
Time frame: 14 days of losartan treatment
Number of Participants With Increase of Supplemental Oxygen Needs From Baseline.
Time frame: 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)
Time frame: 14 days of losartan treatment
Number of Participants With Extracorporeal Membrane Oxygenation Use
Time frame: 14 days of losartan treatment
Number of Participants With Renal Replacement Therapy Use
Time frame: 14 days of losartan treatment
Number of Participants With Intolerance to High Dose (50mg) Losartan After Tolerating 25mg
Time frame: 14 days of losartan treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32658300Smolander J, Bruchfeld A. [COVID-19 and kidney disease]. Lakartidningen. 2020 Jul 13;117:20110. Swedish.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias Salathe principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Losartan in people with COVID-19, run by University of Kansas Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-related Adverse Events as Assessed by Protocol Definition of AE (time frame: 14 days of losartan treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04335123, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2024.