A controlled trial of the drug tranexamic acid (TXA) in inpatients recently admitted to the hospital with the diagnosis of COVID19. 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 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.
Fortunately, 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 UAB, 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 admitted to the regular hospital (non-Intensive Care Unit; ICU)
for the diagnosis of COVID19 is proposed. 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 daily anticoagulation as directed by their primary care team.
The primary endpoint for the study would be a need for transfer to an ICU. Contact would be
daily and via remote processes. Care for the COVID19 patient would otherwise be standard of
care and directed by the primary caretakers of the patient.
Drug: Tranexamic acid
previously described
Drug: Placebo oral tablet
previously described
Inclusion Criteria:
- Positive COVID19 test
- Admission to hospital without immediate plans for Intensive Care Unit transfer
- Age >/= 19 y.o.
Exclusion Criteria:
- Allergic reaction to tranexamic acid
- History or active evidence of hypercoagulation disorders including but not limited to
deep vein thrombosis, pulmonary hypertension, diffuse intravascular coagulopathy
- Preadmission 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