Researchers are now enrolling outpatients with COVID-19 for a randomized controlled trial of the effectiveness of two drug regimens – hydroxychloroquine and hydroxychloroquine with azithromycin.

Hydroxychloroquine has received considerable hype as a potential treatment for COVID-19 and has been confused with chloroquine, a drug stopped in a treatment trial in Brazil. There is conflicting evidence on whether it works, which is why the research team at the University of Washington School of Medicine is conducting a rigorous trial to offer answers.

Today, the FDA released a statement that chloroquine and hydoxychloroquine should be used in supervised settings, like clinical trials, where the potential risks can be better studied and mitigated. In this trial, patients will have heart rhythm monitoring to ensure safety. The trial will also exclude people with underlying cardiac, kidney or liver disease. Another observational study conducted by the Veterans’ Health Administration raised concerns about the safety and efficacy of hydroxychloroquine in hospitalized patients with COVID-19. These patients were not treated in a randomized trial, raising concerns that sicker patients may have received the medication, and making the findings difficult to interpret.

The University of Washington School of Medicine study is seeking people who have tested positive for COVID-19, but who are not sick enough to be in a hospital. Enrollment is for two cohorts – high-risk and low-risk. High-risk outpatients are those over age 60 or with an underlying risk factors, such as diabetes, hypertension, obesity, or lung problems. The low-risk cohort are outpatients age 18 to 59 without any of those conditions. The trial will enroll 630 patients at sites across the country, including University of Washington. Additional sites are planned in Boston, New Orleans, New York, Syracuse, and Chicago.

To enroll, go here.

“We are recruiting patients with recently diagnosed COVID infection and hope to show whether early treatment can keep them from having to be admitted to the hospital,” said co-principal investigator Christine Johnston, associate professor of medicine in the Division of Allergy and Infectious Diseases at the University of Washington School of Medicine. “We are studying whether the early treatment of COVID-19 prevents viral pneumonia and also seeing if the medications decrease viral shedding, which could have a potential benefit of reduced transmission of COVID-19."

The $5.8 million trial is funded by the COVID-19 Therapeutics Accelerator, an initiative launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard, with funding from an array of public and philanthropic donors. The accelator was launched to speed-up the response to the COVID-19 pandemic by funding the identification, assessment, development, and scale up of treatments.

Volunteers in the trial are enrolled into three arms: hydroxychloroquine, hydroxychloroquine with the antibiotic azithromycin, or a placebo.

The study will measure nasal viral shedding by asking study participants to collect daily nasal swabs . The viral shedding pattern will be compared between the different treatments. If a treatment leads to faster clearance of viral shedding, it could theoretically decrease the risk of passing the virus on to others.

If another medicine comes along that looks promising, the trial can test that too, said Johnston.

Hydroxychloroquine is an antiviral medication that has been used since the early 1950s. It’s used to prevent malaria and to treat autoimmune diseases like rheumatoid arthritis and lupus. The medication is hypothesized to work by preventing the virus from entering the cell. Azithromycin is used to treat a wide variety of bacterial infections. It has some activity against many viruses in the lab, but has not been shown to have antiviral activity in people.

Co-principal investigator Jared Baeten, professor of global health at the University of Washington Schools of Medicine and Public Health, said small studies have shown encouraging results using hydroxychloroquine but also no benefit.

"That’s not nearly the kind of evidence that the public needs," he said about small studies. "This rigorous trial will quickly provide the answer whether hydroxychloroquine with or without azithromycin is effective and safe, or whether we should move on to other potential therapies.”

In this trial, volunteers are enrolled by telehealth. They are then asked to collect daily nasal swab for 14 days as well as take their temperature and use a pulse oximeter, a finger-clip which measures oxygen levels in the blood. Another device will monitor their heart rhythm to warn of any cardiac toxicity, one of the serious side effects of hydroxychloroquine and azithromycin.

Over 10 days, those on the drug arms of the trial will be given 400mg of hydroxychloroquine two times a day for the first day and 200mg twice a day for the next nine days. An azithromycin dose of 500mg will be given on the first day of the study, and then 250mg will be given once a day for four more days.

Results of the trial are expected by July. The findings will determine whether a treatment looks promising enough for larger clinical trials and whether the drugs are safe.

Related trial at UW Medicine

The study is teaming with another hydroxychloroquine trial being led by the University of Washington School of Medicine in collaboration with NYU Langone to definitively determine whether hydroxychloroquine can prevent transmission in people exposed to the virus.

The trial looking at post-exposure preventive therapy for COVID-19 is enrolling 2,000 participants referred by physicians at six sites, who are close contacts of persons with confirmed or pending COVID-19 diagnoses. Ruanne Barnabas, associate professor of global health at the University of Washington Schools of Medicine and Public Health, is the principal investigator.

Both trials are part of the COVID-19 Therapeutics Accelerator.

Background of researchers

Johnston has been studying chronic viral infections for 15 years, mostly herpes simplex virus infection. She has done many clinical research studies and antiviral and vaccine clinical trials. Baeten, vice dean of the UW School of Public Health, led one of the large, multisite trials in Africa on the efficacy of Truvada in preventing HIV transmission.

For more information about the study, go to www.covid19treatmentstudy.org.

For more information about the COVID-19 exposure trial, go to www.covid19pepstudy.org.

Researchers answer your questions about hydroxychloroquine: depts.washington.edu/covid19trx/faqs/

Background on the COVID-10 Therapeutics Accelerator: https://www.therapeuticsaccelerator.org/