Antiviral Effects of TXA as a Preventative Treatment Following COVID-19 Exposure (TXACOVIDPREV)

• ClinicalTrials.gov Identifier: NCT04550338
• Recruitment Status: Not yet recruiting
• First Posted: September 16, 2020
• Last Update Posted: February 16, 2021
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): Timothy Ness, MD, University of Alabama at Birmingham

Study Description

Brief Summary:

A recent report in Physiolological Reviews proposed that the endogenous protease plasmin acts on SARS-CoV-2 by cleaving a newly inserted furin site in the S protein portion of the virus resulting in increased infectivity and virulence. A logical treatment that might blunt this process would be the inhibition of the conversion of plasminogen to plasmin. Fortunately, there is an inexpensive, commonly used drug, tranexamic acid, TXA, which suppresses this conversion and could be re-purposed for the treatment of COVID-19. TXA is a synthetic analog of the amino acid lysine which reversibly binds four to five lysine receptor sites on plasminogen. This reduces conversion of plasminogen to plasmin, and is normally used to prevent fibrin degradation. TXA is FDA approved for the outpatient treatment of heavy menstrual bleeding (typical dose 1300 mg p.o. TID x 5 days) and off-label use for many other indications. TXA is used perioperatively as a standard-of-care at UAB for orthopedic and cardiac bypass surgeries. It has a long track record of safety such that it is used over-the-counter in other countries as an antiviral and for the treatment of cosmetic dermatological disorders. Given the potential benefit and limited toxicity of TXA it would appear warranted to perform randomized, double-blind placebo controlled exploratory trial at UAB as a prophylactic antiviral treatment following exposure to COVID-19 in order to determine whether it reduces infectivity and virulence of the SARS-CoV-2 virus as hypothesized. Involvement of each patient is only for 7 days before primary endpoints and 30 days for final data collection.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Tranexamic acid; Drug: Placebo	Phase 3

Detailed Description:

Patients who are self-identified as having had close personal contact with an individual who has tested positive for COVID-19 will be invited to enroll in the study. On Day 1 they will be consented and randomized to one of two arms of the study: Arm 1 will consist of a 5 day treatment with tranexamic acid (TXA; 1300 mg p.o. TID x 5 days) and Arm 2 will consist of a 5 day treatment with an identical appearing placebo. All subjects will be tested using nasopharyngeal RNA swabs for the presence of the SARS-CoV-2 virus on Days 1 and 7. The primary endpoint will be conversion from a negative test for COVID-19 on Day 1, to a positive test on Day 7. Secondary data related to symptoms and co-morbidities will also be gathered.

Subjects who are positive for COVID-19 on Day 1 will not be included in the primary endpoint analysis for this study, but will receive the same 5 days of treatment and their data used for secondary analyses including safety.

All subjects in Arm 1 will also be treated with apixaban (5 mg p.o. BID x 5 days) to mitigate potential risks associated with hypercoagulability which have been noted in COVID-19 patients and which could be made worse with TXA treatment. The subjects in Arm 2 who received placebo in place of TXA will receive a second placebo tablet in place of apixaban.

Patients will be consented via the existent mechanisms associated with outpatient recruitment for all COVID-related studies at UAB. Consent would be performed remotely. All nasopharyngeal swabs will be obtained through the existent mechanisms for COVID-19 testing at UAB. Follow-up would consist of daily phone/internet contact for 7 days unless subjects acquire symptoms consistent with COVID-19, in which case they will be followed until resolution of their symptoms or for a maximum of 30 days.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Placebo-controlled, double-blind, randomized, controlled trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Once patient is consented, pharmacy will randomize to one of two arms and prepare coded sets of drugs
• Primary Purpose: Prevention
• Official Title: Antiviral Effects of Tranexamic Acid (TXA) as a Preventative Treatment Following COVID-19 Exposure
• Estimated Study Start Date: August 1, 2021
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: March 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tranexamic Acid Treatment	Drug: Tranexamic acid; Oral administration of blinded medications
Placebo Comparator: Placebo Treatment	Drug: Placebo; Oral administration of blinded medications

Outcome Measures

Primary Outcome Measures :

1. Conversion from negative to positive COVID-19 test [ Time Frame: Repeat testing after 7 days ]
   RNA testing of nasopharyngeal swabs

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• self-reported close exposure to individuals who test positive for COVID-19 virus

Exclusion Criteria:

• pregnancy, allergy to study drugs, history of hypercoagulability or hypocoagulability, use of anticoagulant medications, seizures, presence of intravascular stents or other instrumentation that may lead to the formation of blood clots

Contacts and Locations

Contacts

Contact: Timothy J Ness, MD PhD; 205-907-9743; tness@uabmc.edu

Sponsors and Collaborators

University of Alabama at Birmingham

More Information

• Responsible Party: Timothy Ness, MD, Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT04550338
• Other Study ID Numbers: TXA.COVID.3
• First Posted: September 16, 2020
• Last Update Posted: February 16, 2021
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: all de-identified data would be available upon request
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: within one month of request
• Access Criteria: institutional approval

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Timothy Ness, MD, University of Alabama at Birmingham:

COVID-19; tranexamic acid; preventative therapy; prophylactic therapy

Additional relevant MeSH terms:

Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants