UAB Clinical Trial Underway for COVID-19 Treatment
By Jane Ehrhardt
UAB is looking for Covid-positive individuals for an outpatient study that examines the effect of a common drug on inhibiting the progression of the disease, especially in people with comorbidities. Devised by Tim Ness, MD, PhD, professor emeritus with UAB Department of Anesthesiology and Perioperative Medicine, the study focuses on dampening the role of plasmin in activating the coronavirus.
The study, titled TXA and Corona Virus 2019 (COVID19) in Outpatients, tests the hypothesis of a paper published online in Physiological Reviews on March 27 by UAB's Sadis Matalon, PhD, and colleagues in Texas and San Francisco. In the research literature they reviewed for the paper, they note that all the comorbidities, such as diabetes, hypertension, cerebrovascular illness, coronary heart disease and chronic obstructive pulmonary disease, feature elevated levels of the protease plasmin.
A biochemical action of plasmin is to cleave little segments of proteins off. This nicking increases infectivity in many viruses. The researchers noted that COVID-19 has such a site on its spike protein, and proposed that plasmin may cleave it, therefore increasing the virus's potency and infectiousness. That made plasmin a promising therapeutic target for combating COVID-19.
"It turns out that when you cleave some of the proteins in the Covid virus, it appears to be able to enter cells more easily and to start its viral processes more easily. It's basically activated," Ness says. "So people with high plasmin levels tended to do worse with the virus."
Ness, however, saw a possible blockade to the plasmin cleaving action. "As an anesthesiologist, I use a plasmin inhibitor on a daily basis, called tranexamic acid (TXA). Almost every cardiac bypass and orthopedic surgery case uses it, because of its action on inhibiting plasmin formation," he says.
TXA is an FDA-approved, inexpensive drug that stops plasmin from converting from its inactive form of plasminogen to the active protease form. "It's over-the-counter in the UK, Japan, and East Asian countries. And in Japan they use it off-label as an antiviral," Ness says. It's approved in the U.S. for treating heavy menstrual bleeding because of its effect on clotting--which is also related to plasmin levels--and is being reviewed for use in Cesarean section surgeries.
"We use TXA because of its antiviral action," Ness says. "TXA doesn't form clots, even though it's used to help with clotting." Plasmin breaks down the protein fibrin which is what forms the clots. TXA inhibits plasmin, thus requiring those in the study to also take a blood thinner to counteract any potential effects from the lowering of plasmin.
Therefore, each patient in the study takes a daily pill for five days of both TXA along with Eliquis--a blood thinner generically known as apixaban. "They counteract each other's potentially bad things, but leaves the antiviral effect of the TXA," Ness says. "We wish TXA had no effect on blood clotting, because that would make it simpler. We wouldn't have to give the second drug to avoid potential problems."
This small, exploratory study of 100 participants is the initial safety and feasibility step to determine whether TXA has some beneficial action for those with the coronavirus. "We need to examine the safety of TXA in this situation because having Covid is not the same as being healthy, and there could an interaction between the drug and the disease processes," Ness says. "That's why this particular study is limited to people who are within the first seven days of their symptoms."
The participants--19 years old and older--are then studied for seven days following the five-day treatment. "We want to find out if TXA can minimize the impact of the subsequent symptoms for people who test positive for COVID-19," Ness says. If the TXA treatment could reduce the infectivity and virulence of the virus, it could lessen the severity of symptoms and the need for lengthy hospitalization, especially those in vulnerable populations with comorbidities.
Ness encourages physicians to pass along the UAB phone number--205-934-6777--to their patients who have recently tested positive for COVID-19. "If physicians have patients wondering if there is something out there, they can call and find out every study available at UAB on Covid right now, of which this is one of them," he says.