Hennepin Healthcare Research Institute (HHRI) and University of Minnesota Medical School researchers have begun enrolling patients in newly launched clinical trials involving a blood pressure medication, losartan, as a potential treatment for those recently diagnosed with COVID-19. Both studies are multi-site trials, one for patients requiring hospitalization and the other for diagnosed patients who do not require a hospital stay.
The first evaluates whether the angiotensin II receptor blocker (ARB) losartan can prevent lung injury in those hospitalized with COVID-19 pneumonia, while the second evaluates if the drug can prevent hospitalizations.
The trial's co-principal investigators are Christopher Tignanelli, MD, assistant professor in the Medical School's Department of Surgery, Division of Critical Care/Acute Care Surgery, and Michael Puskarich, MD, associate professor in the Department of Emergency Medicine at the University and emergency physician at Hennepin Healthcare.
"Losartan has an established safety profile and is readily available," said Tignanelli. "We wanted to test a readily available, cheap, FDA-approved, generic drug with potential efficacy against COVID-19."
The way losartan works is promising because it blocks a receptor, or doorway into cells, that a chemical called angiotensin II uses to raise blood pressure, and in excess, damages the lungs. COVID-19, or SARS-CoV-2, binds to the angiotensin-converting enzyme 2 (ACE2) receptor, preventing it from doing its normal job in breaking down angiotensin II and leading to higher than normal levels. It's possible that losartan might block that extra angiotensin II, stopping lung injury.
"Losartan is different from the other treatments being tested right now - it's not an antiviral medication," said Puskarich. "We're trying to prevent the lung injury caused by the virus that makes it so deadly. We're trying to turn COVID-19 into an everyday coronavirus - the common cold."
The inpatient trial, funded by the COVID-19 Therapeutics Accelerator Funds, takes place in Minnesota at M Health Fairview hospitals and Hennepin Healthcare, as well as at multiple sites nationwide.
The COVID-19 Therapeutics Accelerator is an initiative launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard, with funding from an array of public and philanthropic donors, to speed-up the response to the COVID-19 pandemic by funding the identification, assessment, development and scale-up of treatments.
The outpatient arm of the trial, funded by the Minnesota Partnership, will enroll patients at M Health Fairview hospitals, Mayo Clinic and HCMC.
"No matter how promising an existing drug may appear to be in treating COVID-19, there is only one way to determine safety and effectiveness for patients. And, that is a well-designed clinical trial," said Tim Schacker, MD, vice dean for research at the Medical School and co-investigator of the trial.
Tignanelli and Puskarich, in a correspondence piece published in Lancet Respiratory Medicine, challenged the medical community to investigate if blood pressure medications could be an effective treatment for those with COVID-19. Five weeks later, the team, led by Tignanelli and Puskarich, enrolled the first person in such a study to test their hypothesis. The rapid launch of two more complex clinical trials is another illustration of the ability of the University of Minnesota to rapidly innovate and deploy research aimed at mitigating COVID-19 and its associated risks.