A controlled trial of the drug tranexamic acid (TXA) in outpatients who were recently diagnosed with COVID-19. It is hypothesized that TXA will reduce the infectivity and virulence of the virus.
A recent report in Physiological Reviews proposed that the endogenous protease plasmin acts
on the COVID19 virus by cleaving a newly inserted furin site in the S protein portion of the
virus resulting in increased infectivity and virulence. Patients with hypertension, diabetes,
coronary artery disease, cerebrovascular illness, lung disease and kidney dysfunction
commonly have elevated levels of plasmin/plasminogen and it was proposed that this may be the
mechanism for poorer outcomes in patients with these co-morbidities. A logical treatment that
might blunt this process would be the inhibition of the conversion of plasminogen to plasmin.
There is an inexpensive, commonly used drug, tranexamic acid, (TXA), which suppresses this
conversion and could be re-purposed for the treatment of COVID19.
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 treatment of heavy
menstrual bleeding (typical dose 1300 mg p.o. three times per day x 5 days) and off-label use
for many other indications. TXA is used perioperatively as a standard-of-care at the
University of Alabama at Birmingham (UAB) for orthopedic and cardiac bypass surgeries. At our
institution, it is commonly employed in hemorrhaging trauma patients and currently is being
studied for perioperative use in Cesarean section surgeries. It has also been utilized for
spinal surgery, neurosurgery, orthognathic surgeries and even long term for the treatment of
cosmetic dermatological disorders with a long track record of safety. Given the potential
benefit and limited toxicity of TXA it would appear warranted to perform a rapid randomized,
double-blind placebo controlled exploratory trial at UAB in the treatment of the early phases
of COVID19 to determine whether it reduces infectivity and virulence of the COVID19 virus as
hypothesized. Involvement of each patient is only for 7 days before primary endpoints.
An exploratory, randomized, placebo-controlled, double-blind Phase 2 clinical trial in which
study patients have just been diagnosed with COVID19 as an outpatient. The overall goal of
this exploratory study is to assess both safety and efficacy of 5 days of TXA versus placebo
in the COVID19 population. All patients would also receive apixaban 5 mg p.o. BID. The
primary endpoint for the study would be a need for hospitalization. Contact would consist of
daily phone contact. Care for COVID19 would otherwise be standard of care.
Drug: Tranexamic acid tablets
Oral dosing of 1300 mg p.o. three times per day x 5 days versus identical placebos
Drug: Placebo oral tablet
2 tablets p.o. three times per day x 5 days
Inclusion Criteria:
- Positive COVID-19 test
- Outpatient
- Age >/= 19 y.o.
Exclusion Criteria:
- Allergic reaction to tranexamic acid
- History of hypercoagulation disorders (deep venous thrombosis, pulmonary
thromboembolism)
- Ongoing anticoagulation
- History of GI bleeding
- History of Seizures
- Cardiac or other vascular stents
- History of severe renal disease
- History of intracranial hemorrhage
University of Alabama at Birmingham
Birmingham, Alabama, United States
Timothy J Ness, MD PhD, Principal Investigator
University of Alabama at Birmingham