Clinical trial NCT04338126: Tranexamic Acid (TXA) and Corona Virus 2019 (COVID19) in Inpatients
Official title: Exploratory Studies of the Effect of Tranexamic Acid Treatment on the Progression of COVID19 in Inpatients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: COVID19
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2020-04-08
Enrollment: 0
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled, double blind comparison
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Admission to Intensive Care Unit
timeFrame: Randomization to 7 days after randomization
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Timothy J Ness, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: