Alabama clinical trial to test possible COVID-19 treatments for outpatients

Why is the COVID-19 virus more dangerous in pre-existing sick people?

Sadis Matalon, University of Alabama Birmingham, And a colleague from Texas and San Francisco asked that question with a hypothesis paper They reviewed in detail the research literature on hypertension, diabetes, coronary heart disease, cerebrovascular disease, chronic obstructive pulmonary disease and renal dysfunction, as well as many viral studies and COVID-19 pathology studies. And clinical presentations, and literature on life-threatening acute respiratory distress syndrome.

Twelve days later, UAB emeritus professor Timothiness said ClinicalTrials.gov For an exploratory COVID-19 outpatient study to test the Matalon hypothesis and prevent worse clinical outcomes. His quick reaction is another example of agile UAB researchers during the COVID-19 pandemic.

In a physiological review paper, the researchers pointed out that all these comorbidities are characterized by elevated levels of the extracellular protease plasmin. Plasmin can nick a protein with an amino acid sequence called the furin site. For many viruses, this nick makes them more infectious. Both SARS and MERS – Two virulent coronaviruses associated with the COVID-19 virus – “evolving an unusual two-step furin activation for fusion, suggesting a role in the process of emergence in the human population,” the researchers say. Wrote.

They pointed out that the COVID-19 virus SARS-CoV-2 has a furin site in the spike protein, a protein essential for virus attachment to lung cells. Researchers proposed that plasmin could cleave that site in the spike protein, increasing its infectivity and pathogenicity, “the plasmin system represents a promising therapeutic target to combat COVID-19. There is a possibility”.

Ness is a cheap and commonly used drug that targets plasmin (tranexamic acid, TXA) by inhibiting the conversion of the inactive precursor plasminogen to the active protease plasmin. Already know that there is

TXA is approved by the US Food and Drug Administration for the treatment of menstrual bleeding. This is because the lower the plasmin level, the better the clotting. TXA has a long history of safety and is typically used off label. At UAB Hospital, TXA is used as the standard treatment for orthopedic and cardiac bypass surgery. It is commonly used in patients with hemorrhagic trauma and has been used in spinal surgery, neurosurgery and orthodontic surgery. It is under consideration for use in cesarean section surgery.

for Clinical trialNess et al. have initiated a double-blind study of recently diagnosed COVID-19 outpatients receiving TXA or placebo tablets. Anticoagulants are also given to the patient. The overall goal of the exploratory study is to assess the safety and efficacy of TXA and placebo for 5 days. Registration is in progress.

Nes and colleagues hypothesize that TXA treatment reduces the infectivity and pathogenicity of the virus, as measured by a reduced need for hospitalization within a week if the patient’s condition deteriorates. Adults over 19 years old, all patients – Whether it is in the control group or the TXA group – You will receive standard care as directed by your primary caregiver.

More about Investigation, “Outpatient TXA and Coronavirus 2019 (COVID19)”, Patients and Physicians can Contact Dr. Timothiness. [email protected] Patients who have recently tested positive for COVID-19 can call 205-934-6777 to see if they are eligible for the study.

The other principal investigator in the trial is Dr. Sonya Heath, a UAB professor. Medical school Infectious disease department; UAB associate professor Dr. Brant Wagener and prominent professor Sadis Matalon Anesthesiology and Perioperative Medicine.. Ness is an emeritus professor in that department.

Author of Physiological Review paper“Rising plasmin as a common risk factor for COVID-19 susceptibility” is Hong-Long Ji and Runzhen Zhao at the University of Texas Tyler Health Sciences Center. Michael A. Mathey, University of California San Francisco. And Matalon.

Matalon said the paper is widely known. “It has been downloaded 26,565 times and has been quoted 55 times since it was published online,” he said.

At the UAB, Matalon is chairing the Anesthesiology of the Alice McNeill Endowment Course, a prominent professor and co-chair of the study.