Tranexamic Acid (TXA) and Corona Virus 2019 (COVID19) in Inpatients (TCInpatient)

The University of Alabama at Birmingham

Status and phase: Withdrawn; Phase 2

Conditions: COVID19

Treatments: Drug: Tranexamic acid; Drug: Placebo oral tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT04338126

TXACOVID2

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

Tranexamic Acid Treatment

Experimental group

Description:

Oral dosing of tranexamic acid at dose of 1300 mg p.o. three times per day x 5 days; alternative dosing intravenously with loading dose of 10 mg/kg followed by 1 mg/kg/hr infusion x 5 days

Treatment:

Drug: Tranexamic acid

Placebo Treatment

Placebo Comparator group

Description:

2 tablets of placebo three times per day x 5 days; alternative dosing intravenous normal saline at volumes similar to those use for experimental arm

Treatment:

Drug: Placebo oral tablet