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

Tracking Information

• First Submitted Date: September 13, 2020
• First Posted Date: September 16, 2020
• Last Update Posted Date: February 16, 2021
• Estimated Study Start Date: August 1, 2021
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 13, 2020)

Conversion from negative to positive COVID-19 test [ Time Frame: Repeat testing after 7 days ]

RNA testing of nasopharyngeal swabs

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Antiviral Effects of TXA as a Preventative Treatment Following COVID-19 Exposure
• Official Title: Antiviral Effects of Tranexamic Acid (TXA) as a Preventative Treatment Following COVID-19 Exposure
• 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.

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 Type: Interventional
• Study Phase: Phase 3

Study Design

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

• Condition: COVID-19

Intervention

• Drug: Tranexamic acid
  Oral administration of blinded medications
• Drug: Placebo
  Oral administration of blinded medications

Study Arms

• Experimental: Tranexamic Acid Treatment
  Intervention: Drug: Tranexamic acid
• Placebo Comparator: Placebo Treatment
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: September 13, 2020): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2023
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

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

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04550338
• Other Study ID Numbers: TXA.COVID.3
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

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

• Responsible Party: Timothy Ness, MD, University of Alabama at Birmingham
• Study Sponsor: University of Alabama at Birmingham
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Alabama at Birmingham
• Verification Date: September 2020