New trial evaluates potential COVID-19 treatments in high-risk patients

Researchers from the University of Kentucky are conducting a clinical trial to evaluate the effectiveness of azithromycin, ivermectin and camostat mesylate alone or combined with hydroxychloroquine in high-risk patients with COVID-19.

“While there is no standard treatment for COVID-19, this trial gives us the ability to test multiple therapies rapidly in order to identify the most promising agents,” Susanne M. Arnold, MD, a medical oncologist and associate director of clinical translation at the University of Kentucky’s Markey Cancer Center, said in a press release. “This rapid assessment means that the trial can quickly include and test new therapies as it identifies ones that are not effective.”

The trial is a randomized, multi-arm phase 2 trial that researchers described as having a “pick-the-winner” design, which allows them to quickly learn which treatment is most effective and which require further investigation in a larger, placebo-controlled clinical trial.

Researchers of the trial aim to enroll 240 patients who tested positive for COVID-19 and are hospitalized or recovering at home.

Those included in the trial will have at least one feature that places them at a high risk for serious COVID-19 infection, including diabetes, hypertension, cancer, lung disease, an underlying heart condition or being older than 50 years of age.

Once enrolled, patients will be assigned to receive hydroxychloroquine alone, hydroxychloroquine plus azithromycin, hydroxychloroquine and ivermectin, or camostat mesylate.

According to the press release, these medications were chosen because of their wide availability and existing data suggesting they could be effective treatments for COVID-19.

Hydroxychloroquine is used to prevent and treat malaria as well as rheumatoid conditions, like lupus and rheumatoid arthritis. Last week, WHO temporarily suspended the use of hydroxychloroquine in the Solidarity trial — an international clinical trial launched by WHO and partners to investigate effective treatments for COVID-19 — after data published in The Lancet indicated that patients who used the drug alone or in combination with a macrolide had a higher mortality rate. The trial's Data Safety Monitoring Board is currently reviewing safety data from the Solidarity trial and other ongoing studies to make a definitive decision on whether hydroxychloroquine should continue to be evaluated as a potential treatment for patients with COVID-19. The final decision is expected to be made by mid-June, according to WHO.

Azithromycin is an antibiotic with immunomodulatory effects that is used to treat infections caused by bacteria. Ivermectin is an antiparasitic agent that has shown activity in cellular models in multiple viruses, including equine encephalitis and influenza.

Researchers at the University of Kentucky are among the first to include camostat mesylate — a serine inhibitor used to treat chronic pancreatitis and esophageal reflux in Japan — in their trial. The agent has previously been shown to prevent protein spikes in SARS-CoV-2, which is required for the virus to infect cells.

“The goal is to prevent patients from getting severe cases of the disease that would require hospitalization or put them in the ICU or on a ventilator,” J. Zachary Porterfield, MD, an infectious disease expert, virologist and assistant professor of medicine at the University of Kentucky, said in the release. “No proven therapies have been demonstrated to prevent progression of COVID-19 to severe illness. This is a critical unmet need for high-risk individuals that would also reduce the strain on our health care system.”