Trial of Imatinib for Hospitalized Adults With COVID-19

  • STATUS
    Recruiting
  • End date
    Jun 1, 2023
  • participants needed
    204
  • sponsor
    University of Maryland, Baltimore
Updated on 22 August 2021
covid-19
SARS
oropharyngeal

Summary

This study is a randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19

Description

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and at present with no approved or proven antiviral treatment.

Imatinib is a tyrosine kinase inhibitor that has been approved for treatment of many hematologic and solid neoplasm. Imatinib is a weak base that compared to the extracellular compartment is enriched over 1000-fold in the lysosome within several hours as a result of its lysosomotropic property. Imatinib as a weak base accumulates in lysosomes resulting in some antiviral activities by lysosomal alkalization required for virus/cell fusion.

Imatinib demonstrates in vitro activity against SARS-CoV viruses. Imatinib inhibit SARS-CoV and MERS-CoV with micromolar EC50s (range, 9.8 to 17.6 M) with low toxicity. The mechanism of action studies suggested that ABL-1 tyrosine kinase regulates budding or release of poxviruses and Ebola virus, demonstrating that the c-ABL-1 kinase signaling pathways play an important role in the egress of these viruses. It is also reported that kinase signaling may also be important for replication of two members of the Coronaviridae family, SARS-CoV and MERS-CoV. In vivo studies performed in the mouse model of vaccinia virus infection showed that imatinib was effective in blocking dissemination of the virus.

Imatinib has anti-inflammatory activity including its effectiveness in a "two-hit" murine model of acute lung injury (ALI) caused by combined lipopolysaccharide (LPS) and ventilator-induced lung injury (VILI). Imatinib significantly decreased bronchoalveolar lavage protein, total cells, neutrophils, and TNF levels in mice exposed to LPS plus VILI, indicating that it attenuates ALI in this clinically relevant model. In another experiment, imatinib attenuated ALI when given 4 hours after LPS, suggesting potential efficacy when given after the onset of injury. Overall, these results strongly suggest the therapeutic potential of imatinib against inflammatory vascular leak and a potential role of imatinib combination therapy for patients with acute respiratory distress syndrome (ARDS) on mechanical ventilation.

The investigators hypothesize that addition of imatinib to the best conventional care (BCC) improves the outcome of hospitalized adult patients with COVID-19. This hypothesis is on the bases of 1) intralysosomal entrapment of imatinib will increase endosomal pH and effectively decrease SARS-CoV-2/cell fusion, 2) kinase inhibitory activity of imatinib will interfere with budding/release or replication of SARS-CoV-2, and 3) because of the critical role of mechanical ventilation in the care of patients with ARDS, imatinib will have a significant clinical impact for patients with severe COVID-19 infection in Intensive Care Unit (ICU).

Details
Condition *COVID-19, Covid-19
Treatment Imatinib, Placebo Oral Tablet
Clinical Study IdentifierNCT04394416
SponsorUniversity of Maryland, Baltimore
Last Modified on22 August 2021

Eligibility

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note