A team of University of Michigan physician-researchers have launched a clinical trial of a drug they believe may address the deadly blood clots that form in some patients with COVID-19.
The trial is the first COVID-related investigation to be initiated by Michigan Medicine scientists. The trial is based on the results of a blood inflammation study conducted by the same team using blood samples from Michigan Medicine patients with COVID-19. It is underwritten by the U-M’s Taubman Institute, which makes research grants to clinician-scientists.
Researchers at U-M are cooperating in other COVID studies, but those were established by other institutions.
The U-M study will assess the effects of dipyridamole, a well-tolerated medication approved by the FDA to reduce blood clotting and stroke. It will be administered for 14 days to adult trial subjects who test positive for COVID-19 and are ill enough to be hospitalized.
Yogen Kanthi, MD, and Jason Knight, MD, PhD, are the principal investigators of the trial. Dr. Kanthi is a cardiologist and vascular medicine specialist whose research focuses on how inflammation leads to blood clots. Dr. Knight is a rheumatologist who studies the interplay between the immune system and blood clotting. Both physicians serve on the faculty of the University of Michigan Medical School.
They hope to show that dipyridamole can ameliorate the “storm” of white blood cell activation and blood clotting that has been reported in many patients with COVID-19. The clotting causes complications ranging from stroke to clogged vessels in the lungs that hamper a patient’s oxygenation.
Blood clotting and the related inflammation is a normal part of the body’s response to injury, but scientists are perplexed by the excessive immune response in many COVID-19 patients, in which the beneficial process becomes exaggerated and harmful.
This Michigan Medicine research team, which also includes rheumatologist, Dr. Yu (Ray) Zuo, recently discovered a particular form of inflammation in patients with COVID-19 (1). The research team then searched for FDA-approved drugs that could suppress this specific type of inflammation. They identified dipyridamole as a strong candidate to treat patients with COVID-19.
This is the first COVID-19 trial based on science discoveries made at Michigan Medicine.
“Dipyridamole may suppress the harmful inflammation and blood clotting that intensifies COVID-19 and contributes to death,” said Dr. Zuo.
The investigators plan to enroll 80 patients in the randomized drug trial, which opened in May and will likely run through December 2020. Patients will receive 100 milligrams of dipyridamole, four times per day, for two weeks. Some participants will receive an inert placebo.
Blood samples from patients will be studied for the presence of D-dimer, a protein that appears when blood clots dissolve. The team will also study proteins and cells isolated from patient blood in hopes of better understanding the body’s response to COVID-19.
“While we will follow levels of D-dimer as the primary readout of the study, we are also of course very interested in the extent to which dipyridamole may improve overall outcomes. In fact, we are actively looking to bring this trial to other centers, which could give us the numbers we need to make definitive statements about clinical outcomes.” said Dr. Kanthi.
For more information about the study, visit https://clinicaltrials.gov/ct2/show/NCT04391179