University of Minnesota researchers expect to finish enrollment this week in the nation's first clinical trial of ivermectin to treat COVID-19, and the study's highly anticipated results could be only a month away.
The COVID-OUT study is reviewing three common drugs, including the antidepressant fluvoxamine and the diabetes treatment metformin, but gained attention for its inclusion of ivermectin. The controversial drug has been championed by opponents of COVID-19 vaccines, despite a warning from the Food and Drug Administration (FDA) that ivermectin is cleared only to treat parasitic infections, head lice and certain skin conditions.
Anti-inflammatory benefits of all three medications prompted the U study, which was delayed by slow enrollment over the summer until the delta and omicron waves of the pandemic emerged. Lead researcher Dr. Carolyn Bramante said the results will provide clinical guidance to doctors who are facing record pandemic cases and to the FDA about whether to authorize the drugs for treatment of COVID-19.
"Sooner would have been better, but I'm really proud of my team," she said. "We will be done very quickly."
Proven outpatient COVID-19 treatments have been limited, and supplies in Minnesota have been scarce. Providers in the state discontinued two types of monoclonal antibody infusions in December because they were ineffective against the omicron variant, and providers had to ration the effective types. New antiviral COVID-19 pills that have received emergency FDA approval are coming in small shipments every other week to Minnesota.
Good news came Tuesday when the state reported its first decline in a month in the positivity rate of COVID-19 testing. Just over 23% of samples were positive in the seven days ending Jan. 14. Modeling by Mayo Clinic suggests a peak is only days away for a pandemic wave that has produced record infections in Minnesota.
A report Tuesday by the Centers for Disease Control and Prevention (CDC) also verified that omicron has produced elevated infections and hospital admissions in the U.S. but shorter hospital stays and fewer intensive care unit admissions and deaths.
Minnesota's experience matches those findings: COVID-19 hospitalizations increased in early January but declined last week and reached 1,507 on Monday. The share of hospitalizations requiring stays in intensive care units also declined from 25% in mid-December to 15%.
The CDC report cautioned that more vaccinations and preventive therapies are needed, because the pandemic continues to threaten hospital capacity and cause COVID-19 deaths.
Minnesota on Tuesday reported 35,504 coronavirus infections and 37 COVID-19 deaths, reflecting pandemic activity over the weekend and some catchup on a backlog of infection reports. While 82% of the state's 11,230 COVID-19 deaths were among seniors, Tuesday's report included the death of a Hennepin County resident age 25-29.
The U trial is enrolling 1,100 patients with COVID-19 to receive fluvoxamine and ivermectin, alone or in combination with metformin, or a nonmedicating placebo for comparison. The study is tracking whether patients taking the drugs for 14 days avoid hospitalization and maintain healthy blood oxygen levels.
Bramante said the drugs have potential to reduce excessive inflammation — a hallmark of some of the most severe and fatal COVID-19 cases. Ivermectin has been tried in other countries, such as India, with less access to vaccine, despite a World Health Organization warning against its use outside clinical trials until its benefits are proven.
Some global studies of the drug have been debunked while others in the U.S. are behind the U study. Duluth-based Essentia Health on Monday announced it was joining the ongoing national ACTIV-6 clinical trial that is studying ivermectin in combination with fluvoxamine and fluticasone, an inhaled steroid.
"The aim of the study is to see if these medications make you feel better sooner and prevent hospitalization," said Dr. Rajesh Prabhu, an Essentia infectious disease specialist.
Bramante is not allowed to see the patient data from the U study until after enrollment is finished, but she said it is a positive sign that a data safety monitoring board has allowed it to continue. That means the drugs aren't causing harm but also there is no proof yet they absolutely work or don't work against COVID-19.
The U has been a national leader in studies to repurpose drugs against COVID-19, launching trials that failed to support the use of hydroxychloroquine for prevention or treatment.
If the COVID-OUT drugs are going to work, Bramante said, they likely need to be taken early in infections. U researchers have been making daily runs to an overnight shipping depot to get study drugs to people with COVID-19 who enroll in less than one day.
Minnesota learned Monday that it will receive a slight increase in proven outpatient treatments. Next week's federal allotment of monoclonal antibodies increased 21% and will include 792 courses of sotrovimab and 1,224 courses of Evusheld, which is mostly limited to COVID-19 patients who are immunocompromised.
Next week's shipment of antiviral pills will be unchanged, with 5,440 doses of molnupiravir and 1,360 doses of the more effective Paxlovid.
M Health Fairview has administered 160 doses of the drugs but has found a 30% refusal rate because people are worried about side effects or don't think their symptoms merit treatment until it is too late, said Dr. Bryan Jarabek, Fairview's chief medical informatics officer.
"People don't realize how sick they're going to get," he said.
Some patients balk at being offered the less effective molnupiravir because the most effective one is being rationed for the highest-risk patients, Jarabek added.
"It is still totally worth it," he said. "It decreases your hospital risk by 30%. It makes you feel better faster."