A team at the University of North Carolina at Chapel Hill is conducting a randomized clinical trial on the effectiveness of hydroxychloroquine in preventing novel coronavirus infections in U.S. health care workers. The study is funded by the Patient-Centered Outcomes Research Institute (PCORI), which hosts an established network of 850,000 clinicians and hundreds of health care systems. UNC is one of 18 sites participating.
Hydroxychloroquine is a drug used to treat malaria, lupus, and rheumatoid arthritis. Some successful cell studies have showed its effectiveness in treating the SARS coronavirus — a different strain of the current virus causing COVID-19 — a few years ago, according to Ross Boyce, who is leading the study at UNC. A paper released in Cell Research in March provided positive results regarding the drug’s effectiveness for treating the novel coronavirus.
But the drug has become politically charged. While President Trump has promoted the use of hydroxychloroquine and has reportedly taken it to prevent contraction of the virus, studies examining the drug when used to treat SARS-CoV-2 infection have, generally, not shown significant efficacy, and clinicians have become more hesitant to administer it.
The FDA has since revoked the emergency use authorization for hydroxychloroquine to treat currently infected patients as it may contribute to heart rhythm problems, blood and lymph system disorders, kidney injuries, and liver problems and failure. More high-quality information on the effectiveness of the drug to prevent infection among healthy but at-risk individuals is needed — a body of knowledge Boyce and his team hope to add to.
Hydroxychloroquine works differently from other drugs being tested such as remdesivir, an antiviral that stops the virus from replicating. Boyce, an infectious disease researcher who specializes in malaria, stresses the study is testing the antimalarial’s potential as a preventative measure versus a treatment for COVID-19.
“What we know from the influenza world is that, once a virus has set in and is replicating at high levels, drugs to treat it are not as effective,” he says. “But if you can get the drug early on, or before the virus sets in, maybe it has some effect there — and maybe you’ll need less of it.”
When used to prevent malaria, only one dose of hydroxychloroquine per week is necessary. But for someone who already has the illness, multiple doses need to be taken each day, Boyce points out.
For the study, a dose of hydroxychloroquine similar to what’s given to people with rheumatoid arthritis will be administered to health care workers who could potentially be exposed to COVID-19. This includes not only doctors and nurses but various technicians and maintenance staff who work in emergency rooms, ICUs, or active hospital floors. The study has recently expanded to include EMS personnel, workers in congregate living settings, and dentists.
“We want to protect our workforce,” Boyce says. “If 20 or 30 percent of health staff get infected or sick, then that’s just as bad as losing ventilators or ICU beds. There’s a limited number of patients we can care for at any time, and if a doctor gets sick, that’s less people we can care for.”
Potential participants will sign up via a national registry of healthcare workers, which will serve as the entry point to undergo screening to rule out preexisting health problems such as asthma and heart disease. After the screening process, those who are eligible visit a drive-through site at UNC Hospitals for testing and are administered either a low dose of hydroxychloroquine or a placebo for 30 days. During this time, they will complete online surveys about symptoms and their response to the medication. At the end of 30 days, they will stop taking the drug and undergo another round of lab tests. They will fill out a survey at the 60-day mark to assess their health after taking the drug.
The benefit of testing existing drugs already on the market, according to Boyce, is that most of the side effects are known and it’s relatively easy to increase production. The downside is the potential for misinformation.
“There’s already been pretty widely publicized runs of some of these drugs,” Boyce says. “People are getting them through either official or unofficial sources and are taking them when we don’t know for sure if there’s really any benefit.”
The fast-paced, widespread nature of this study should shed light on hydroxychloroquine’s effectiveness for fighting COVID-19. Boyce and his team will release their data for analysis along the way in order to uncover information about the drug as quickly as possible.
“The ability of the university and support systems to shift gears and respond to this crisis is a pretty amazing thing,” Boyce says. “Everyone wants to be involved — and people are putting themselves out there to do that.”
Ross Boyce is an assistant professor in the Division of Infectious Diseases within the UNC School of Medicine.