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An Open Label Phase 1 Trial of Losartan for Worsening Respiratory Illness in COVID-19

Trial Profile

An Open Label Phase 1 Trial of Losartan for Worsening Respiratory Illness in COVID-19

Status: Recruiting
Phase of Trial: Phase I

Latest Information Update: 27 Apr 2020

At a glance

  • Drugs Losartan (Primary)
  • Indications COVID 2019 infections; Respiratory insufficiency; Severe acute respiratory syndrome
  • Focus Adverse reactions
  • Most Recent Events

    • 08 Apr 2020 New trial record

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 2019 infections treatment -
Respiratory insufficiency treatment -
Severe acute respiratory syndrome treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 50

  • 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 : 25 Mar 2020

  • Primary Completion Dates

    Planned : 01 Sep 2020

  • End Dates

    Planned : 01 Oct 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
caguiar@kumc.edu
show details
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
msalathe@kumc.edu
show details
-
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
27 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 27 Apr 2020
08 Apr 2020 New trial record New trial record Updated 08 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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