An Open Label Phase 1 Trial of Losartan for Worsening Respiratory Illness in COVID-19
Latest Information Update: 04 Nov 2021
At a glance
- Drugs Losartan (Primary)
- Indications COVID-19 respiratory infection; Respiratory insufficiency
- Focus Adverse reactions
- 02 Nov 2020 Status changed from recruiting to completed.
- 08 Apr 2020 New trial record
Most Recent Events
Trial Overview
Purpose
This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19.
Primary Endpoints
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
Other Endpoints
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
Incidence of mechanical ventilation use
description: Incidence of mechanical ventilation use
time_frame: 14 days of losartan treatment
Days on mechanical ventilation
description: Days on mechanical ventilation
time_frame: 14 days of losartan treatment
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
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
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
ICU length of stay (days)
description: ICU length of stay (days)
time_frame: 14 days of losartan treatment
30-day mortality rate
description: 30-day mortality rate
time_frame: 30 days after diagnosis of COVID-19
Hospital length of stay (days)
description: Hospital length of stay (days)
time_frame: 14 days of losartan treatment
Cumulative incidence of severe adverse events
description: Cumulative incidence of severe adverse events
time_frame: 14 days of losartan treatment
Cumulative incidence of adverse events
description: Cumulative incidence of adverse events
time_frame: 14 days of losartan treatment
Change from baseline in oxygenation
description: Change from baseline in oxygenation
time_frame: 14 days of losartan treatment
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
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
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
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 [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| COVID-19 respiratory infection | treatment | - |
| Respiratory insufficiency | treatment | - |
Biomarker
| NCT Number | Biomarker Name | Biomarker Function |
|---|---|---|
| NCT04335123 | Norepinephrine | Eligibility Criteria |
Subjects
- Subject Type patients
-
Number
Planned: 50
Actual: 34
- Sex male & female
- Age Group ≥ 18 years; adult
Patient 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.
Patient 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.
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04335123 | ClinicalTrials.gov: US National Institutes of Health |
| STUDY00145514 | - |
Trial Dates
-
Initiation Dates
Actual : 04 Apr 2020
-
Primary Completion Dates
Planned : 01 Sep 2020
Actual : 21 Jun 2020
-
End Dates
Planned : 01 Oct 2020
Actual : 17 Aug 2020
Other Details
- Design open; prospective
- Phase of Trial Phase I
- Location USA
- Focus Adverse reactions
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| LosartanPrimary Drug | Oral | Tablet |
Open Label Losartan
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 (25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion) Other Name: Cozaar
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
|
Carolina Aguiar
9139459295
show details
caguiar@kumc.edu |
University of Kansas Medical Center | USA |
| Charles Bengtson, MD | University of Kansas Medical Center | USA |
| Lewis Satterwhite, MD | University of Kansas Medical Center | USA |
| Matthias Salathe | University of Kansas Medical Center | USA |
|
Matthias Salathe, MD
9135886000
show details
msalathe@kumc.edu |
-
|
|
| Usman Nazir, MD | University of Kansas Medical Center | USA |
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| - |
-
|
-
|
| University of Kansas Medical Center |
-
|
-
|
| University of Kansas Medical Center | Kansas City, Kansas | USA |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 10 May 2021 | Biomarker Update | Biomarkers information updated Updated 04 Nov 2021 |
| 04 Nov 2020 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 04 Nov 2020 |
| 02 Nov 2020 | Status change - completed | Status changed from recruiting to completed. Updated 04 Nov 2020 |
| 08 Apr 2020 | New trial record | New trial record Updated 08 Apr 2020 |
References
-
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov
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