‘Rescue Study’ Analyzes if a Protective Substance in the Blood Vessels Can Impact COVID Infections

The University of Minnesota Medical School is participating in a national study to investigate a novel approach in treating COVID-19 by improving the function of blood vessels. The Rescue Study is happening at M Health Fairview St. Joseph's Hospital and seeks to determine if early administration of an endothelial protective substance, Razuprotafib, reduces the severity of COVID-19 lung disease, shortens the need for hospitalization, reduces the need for ventilator support and modifies the inflammatory and blood-clotting effects of the novel coronavirus. 

The Rescue Study is funded by the Department of Defense through a grant awarded to Aerpio Pharmaceuticals. It is being carried out at a limited number of sites around the country. Six people wrote the study’s protocol with experts from the Medical School contributing intellectual capital to its parameters.  

Marc Pritzker, MD, FACC, professor in the Department of Medicine’s Cardiovascular Division, is a primary investigator for the study. He graduated from the Medical School in 1976, before completing an Internal Medicine residency in 1980 and a Cardiovascular Disease fellowship in 1983 — both at the Medical School. Dr. Pritzker is working in tandem with co-investigators Craig Weinert, MD, MPH, professor, and Hem Desai, MBBS, MPH, assistant professor, both in the Department of Medicine’s Division of Pulmonary, Allergy, Critical Care and Sleep Medicine.

What is the Endothelium?

The study analyzes a drug that impacts the endothelium — a thin membrane that lines the inside of blood vessels. The coronavirus has been found in the endothelium, which offers an explanation for the many, diverse manifestations and locations of COVID-19-associated disease.  

“The novel concept here is that moving the endothelium towards its normal, quiescent state may reduce the fluid that floods the lung as well as quiet the inflammatory and blood-clotting stimuli that the virus induces,” Dr. Pritzker said. 

The endothelium reaches every interface between the outside of the body and its internal structures. Normally, endothelial cells release substances that control vascular relaxation and contraction, in addition to enzymes that control blood clotting, immune function and platelet adhesion. COVID-19 disrupts much of this functioning, damaging the endothelium and subsequently resulting in uncontrolled inflammation, clotting and death of regulatory endothelial cells.

How the Trial Works

Trial participants must have had a positive COVID-19 test and be admitted to St. Joseph’s Hospital. Each trial participant receives a series of Razuprotafib injections. The study has incremental “stop-and-look” phases built into it so that a data safety monitoring board can look for evidence of efficacy and potential harm among participants. 

“The other benefit of this is that it isn’t something I just whipped up in the garage with my chemistry set. This drug has been given to over 500 patients for other reasons, so we already have some knowledge of a safety profile,” Dr. Pritzker said.

The findings could prove invaluable for a host of other conditions that elicit similar bodily responses to COVID-19. There are many different infections that lead people to develop COVID-19-like manifestations. Scrub typhus, which affects millions of people in South Asia, has been shown in animal models to adversely promote molecular substances that Razuprotafib antagonizes. While it is a bacterial disease, scrub typhus has a natural history similar to COVID-19-associated disease. 

“It’s not clear how long the vaccine is going to last, so we may continue to have episodes of infection beyond the vaccine, which may only last nine or 10 months. Nobody knows right now. We need to understand what is going to be effective for dealing with infection, whether it’s this one or the next one, and our blood vessel hypothesis will be important for not only this infection but also for whatever other kind is coming,” Dr. Pritzker said.

Understanding the scientific underpinnings will inform future clinical care and provide an opportunity for treatment in areas that lack access to a vaccine. With vaccine distribution being such a logistical challenge throughout the world, Razuprotafib could provide an alternative, and hopefully, effective option for treatment. 

“We have an opportunity and probably an obligation to help the rest of the world that isn’t going to be able to afford the vaccine. If we prove that the blood vessel hypothesis is reasonable, then there is potential to repurpose drugs that exist and are off-patent, meaning they’re much more affordable and can be used to modify the course of diseases around the world. It’s about proving a hypothesis and opening a new door to treat diseases by normalizing the blood vessels,” Dr. Pritzker said.

Lastly, researchers will follow up with study participants as outpatients to examine if drug administration reduces longer-term complications of COVID-19 infection, which is still an important unknown.

“Next steps will depend on the information. If it’s unbelievably successful in demonstrating that it meets the end points of safety and efficacy, then who knows where it will go. The blood vessel hypothesis has a lot of uses in other diseases that have huge unmet needs, such as liver disease, vasculitic diseases, lupus and cerebral malaria, just to name a few,” Dr. Pritzker said.