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University medical team to participate in clinical trial of experimental coronavirus treatment

A team of physicians, infectious disease experts and research supervisors joined the NIH-lead clinical trial of remdesivir to determine its effectiveness in treating COVID-19

<p>Researchers recognize that the remdesivir trial is only the beginning of the University’s attempts to fight coronavirus.</p>

Researchers recognize that the remdesivir trial is only the beginning of the University’s attempts to fight coronavirus.

As coronavirus continues to ravage the world, the U.S. federal, state and local governments are responding with increasingly drastic measures to stem further spread of the pandemic. Last week began with Virginia Governor Ralph Northam issuing stay-at-home orders until June 10 and ended with the Centers for Disease Control and Prevention recommending citizens wear facemasks in public. Yet, despite medical institutions scrambling to develop methods of treatment for the highly contagious and deadly disease, another week has come and gone without approval for a standard treatment for COVID-19.

However, advancements are still underway as last week also brought reports of efforts to combat coronavirus, from doctors and nurses working daily to care for coronavirus patients to updates on experimental treatments. The University Health System announced Thursday that it will participate in an ongoing clinical trial to determine the efficacy of the drug remdesivir in treating COVID-19. 

Remdesivir was a drug originally created to treat the Ebola and Marburg viruses. However, subsequent testing revealed the drug’s ability to treat viruses with similar mechanisms of replication, including Middle Eastern respiratory syndrome and severe acute respiratory syndrome — members of the coronavirus family viral illnesses that result in respiratory tract infections.

The National Institutes of Health through the National Institute of Allergy and Infectious Diseases joined with Gilead Sciences, Inc., a biopharmaceutical company that manufactures remdesivir, to repurpose remdesivir for coronavirus patients. The trial began in February at the University of Nebraska Medical Center in Omaha and now consists of more than 60 institutions and 700 patients internationally.

Dr. Patrick Jackson, assistant professor in the division of Infectious Diseases and International Health, leads the University branch of the remdesivir clinical trial as the principal investigator. Dr. Taison Bell, assistant professor of medicine in the divisions of Infectious Diseases and International Health and Pulmonary and Critical Care Medicine, will act as a co-principal investigator for the University trial.

“Social distancing and washing our hands are great things we should do, but people are looking for more that can be done,” Bell said. “It makes people, especially our patients, feel better knowing we have a medication we can give them that might help them recover.”

Over a maximum of 10 days, hospital personnel will intravenously administer remdesivir to half of the coronavirus patients, while they supply the other half with a placebo — a fluid that resembles remdesivir but does not offer any of its physiological benefits. In order to eliminate any biases in the trial, patients are randomly assigned to either the experimental or the control group, and neither the patients nor the physicians know which individuals receive the drug.

“When scary diseases like this pop up, people might have a tendency to toss drugs at it we think might work even if the evidence isn’t solid,” Bell said. “What we really need are randomized placebo trials to get an accurate sense of whether or not the drug works, how well it works and balance that with toxicity.”

Beyond being randomized and double-blind, the trial has adopted an adaptive format.  Such trials evolve based on feedback that an independent data and safety monitoring board receives. If, for example, remdesivir improved coronavirus patients’ condition, then clinicians would convert remdesivir to act as the control state. The intervention group would either receive remdevisir and another drug that may provide additional therapeutic benefits or a different medication in clinical trials with coronavirus patients, such as hydroxychloroquine, a treatment for malaria, lupus and arthritis. This experimental design allows clinicians to adjust the study in real-time and to optimize treatment options.

University doctors kicked off the trial on the evening of April 1, and just hours later, they enrolled their first patient through the University Health System. Several other individuals have agreed to participate in the past few days, though the health system cannot disclose the exact number to the public at this time.

NIH guidelines state adult patients eligible for the study must exhibit severely compromised lung function indicated by abnormal chest X-rays or the need for supplemental oxygen or a ventilator.

Prior to University involvement in the NIH-Gilead trial, and before coronavirus ever arrived in Charlottesville, the University Health System assembled a team of physicians, infectious disease experts, pharmacists and clinical research supervisors to plan for the nearly inevitable spread of the disease to the community.

According to Jackson, the team formed to coordinate the University Health System’s response to the care of coronavirus patients and to investigate viable treatment options. He credited the team, along with Dr. Amy Mathers and lab director Mendy Poulter, who developed the University’s rapid coronavirus test, as instrumental in the health system’s efforts.

“When we started hearing about COVID-19 infections, we began to prepare even before the first patient walked in the door,” Jackson said. “We put together a group … to analyze how to protect patients and other people in the hospital, as well as to be in a good position to participate in one of these clinical trials.”

A number of candidate therapies emerged from investigations in academia and the private and public sectors, among them remdesivir, hydroxychloroquine and monoclonal antibodies, or proteins that act as part of the body’s immune response to recognize and kill coronavirus. 

Ultimately, based on the available information on each treatment’s effectiveness and versatility, Bell said the University Health System cohort concluded remdesivir was the most promising because of its ability to target the cellular machinery the coronavirus requires to proliferate. 

Jackson agreed that remdesivir has potential, but also emphasized that the remdesivir trial was only the beginning of the University’s attempts to fight coronavirus.

“No one really knows what a good treatment is or what the risks of some of the medications are, so it would be exciting to get more clinical trials to gather data,” Jackson said. “We already have other groups at U.Va. talking about getting more clinical trials together to gather data.”

One potential wrinkle with remdesivir is that the Food and Drug Administration has not approved it for widespread use in coronavirus patients, so the only way to access the drug is through clinical trials or compassionate care for critically-ill patients. Nevertheless, clinicians remain optimistic that if remdesivir helps check coronavirus, the FDA will accelerate the approval process as they have done for hydroxychloroquine in critical COVID-19 cases, allowing Gilead to market remdesivir and doctors to distribute it.

“The FDA has engaged in some emergency approvals lately, and if there is a positive result in this trial, then I think the FDA will move quickly to do the same for remdesivir,” Jackson said.

At this point, there is little certainty if a rapid approval process for remdesivir will be necessary. Clinical trials exploring medications and therapeutic procedures spanning the globe are still in full swing, and there is no conclusive evidence yet that remdesivir is the best treatment doctors can offer.

Jackson and Bell recognize, though, that the significance of the trial lies not in being the ones to discover the correct treatment for coronavirus. Simply contributing data about the advantages — or lack thereof — for various therapies will help researchers at the University and beyond know where to focus their limited time and resources.

“The most important thing right now is to get good data about what works and what is safe, and to do it as quickly as possible,” Jackson said.

According to Jackson, whether it is remdesivir, another drug, or a different method of care entirely, the value in their work stems from the progress made towards finding a solution to the pandemic and providing encouragement to people along the way.

“I am a scientist, so I always want to be careful about making claims about medications, and I won’t be sure until results come back, but I hope remdesivir works,” Bell said. “The thing people really want and need right now, though, is hope that we can do something to stem the tide of coronavirus.”