US Pharm. 2020;45(4):28-32.
Researchers at the Massachusetts Institute of Technology (MIT) and the University of Colorado at Denver have proposed a stopgap measure that they believe could help COVID-19 patients who are in acute respiratory distress. By repurposing a drug that is now used to treat blood clots, they believe they could help people in cases where a ventilator is not helping or where it is not available.
Three hospitals in Massachusetts and Colorado are developing plans to test this approach in severely ill COVID-19 patients. The drug, a protein called tissue plasminogen activator (tPA), is commonly given to heart-attack and stroke victims. The approach is based on emerging data from China and Italy that COVID-19 patients have a profound disorder of blood clotting that is contributing to their respiratory failure.
“If this were to work, which I hope it will, it could potentially be scaled up very quickly, because every hospital already has it in their pharmacy,” said Michael Yaffe, a David H. Koch Professor of Science at MIT. “We don’t have to make a new drug, and we don’t have to do the same kind of testing that you would have to do with a new agent. This is a drug that we already use. We’re just trying to repurpose it.”
Dr. Yaffe, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and an intensive care physician at Boston’s Beth Israel Deaconess Medical Center/Harvard Medical School, is the senior author of a paper describing the new approach. The paper, published in the Journal of Trauma and Acute Care Surgery, was coauthored by Christopher Barrett, a surgeon at Beth Israel Deaconess and a visiting scientist at MIT; Hunter Moore, Ernest Moore, Peter Moore, and Robert McIntyre of the University of Colorado at Denver; Daniel Talmor of Beth Israel Deaconess; and Frederick Moore of the University of Florida.
In one large-scale study of the COVID-19 outbreak in Wuhan, China, it was found that 5% of patients required intensive care and 2.3% required a ventilator. Many doctors and public health officials in the U.S. worry that there may not be enough ventilators for all COVID-19 patients who will need them. In China and Italy, a significant number of the patients who required a ventilator went on to die of respiratory failure, despite maximal support, indicating that there is a need for additional treatment approaches.
The treatment that the MIT and University of Colorado team now proposes is based on many years of research into what happens in the lungs during respiratory failure. In such patients, blood clots often form in the lungs. Very small clots called microthrombi can also form in the blood vessels of the lungs. These tiny clots prevent blood from reaching the air spaces of the lungs, where blood normally becomes oxygenated.
The researchers believe that tPA, which helps to dissolve blood clots, may help patients in acute respiratory distress. A natural protein found in our bodies, tPA converts plasminogen to an enzyme called plasmin, which breaks down clots. Larger amounts are often given to heart-attack patients or stroke victims to dissolve the clot causing the heart attack or stroke.
Animal experiments, and one human trial, have shown potential benefits of this approach in treating respiratory distress. In the human trial, performed in 2001, 20 patients who were in respiratory failure following trauma or sepsis were given drugs that activate plasminogen (urokinase or streptokinase, but not tPA). All of the patients in the trial had respiratory distress so severe that they were not expected to survive, but 30% of them survived following treatment.