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The controversial drug ivermectin failed in a large U.S. trial to reduce COVID-19 hospitalizations and deaths, but a University of Minnesota co-investigator said it warrants continued study because it might shorten the duration of illness.

The results from the ACTIV-6 trial are another strike against ivermectin, despite hope early in the pandemic that it would be a low-cost and abundant COVID-19 therapy. Skeptics of COVID-19 vaccines have been particularly strong proponents.

There were 10 COVID-19 deaths or hospitalizations among the 817 participants who took ivermectin and nine among the 774 people who took non-medicating placebo pills for comparison, according to the ACTIV-6 results, which were published online Sunday evening. ER and urgent care visits were comparable as well.

"Ivermectin is not an effective therapy for COVID-19 at this dose and duration, regardless of what the people promoting or selling ivermectin say," said Dr. David Boulware, a U infectious disease researcher who oversaw the design of ACTIV-6 as co-chair of its protocol committee. "This is now the second very large trial to show no benefit of ivermectin."

The results are not a strike out, though, because people with COVID-19 who took the drug appeared to recover a half-day faster on average than those who took placebos. Those length-of-illness results weren't statistically significant but maintain the possibility that people could benefit from ivermectin, which received federal approval in 1996 as safe and effective to treat parasitic infections.

A new arm of ACTIV-6 is examining a 50% higher dosage taken over six days rather than the three days used for the latest results. ACTIV-6 is a federally funded study, based at Duke University, to determine if existing drugs could be repurposed against COVID-19. The University of Minnesota is one of its leading sites, enrolling 252 participants.

Boulware said he expects ivermectin proponents to dismiss the latest results because of the lower dosage, but that they are "moving the goalpost" because he consulted with some of them at the outset of ACTIV-6 in early 2021 and they supported the dosage at that time.

Calls for a higher dosage grew after a large Brazilian trial similarly showed no benefit against COVID-19. The ACTIV-6 report cited the spotty history of ivermectin research, highlighting three studies that were retracted after initially showing some effectiveness against COVID-19.

Hopes of a benefit drove at least a modest increase in prescriptions. Blue Cross and Blue Shield of Minnesota and its pharmacy benefit manager, Prime Therapeutics, reported 1,300 prescriptions for ivermectin in 2021 — up 50% from 2020.

Taking chances on ivermectin might have been understandable earlier in the pandemic, but Boulware said that isn't necessary now that antiviral pills and monoclonal antibody infusions are proven to work and growing in supply.

Minnesota last week launched a federal test-to-treat program at its Brooklyn Park COVID-19 testing site, where people at risk of severe illness can receive immediate access to antiviral prescriptions. Testing sites in Duluth and Moorhead will add this option this week.

The study results come amid a decline in a spring pandemic wave in Minnesota, where the seven-day average of newly diagnosed coronavirus infections has dropped from 2,100 per day in mid-May to less than 1,700 per day.

True to form with earlier pandemic waves, the number of COVID-19 hospitalizations peaked two weeks after case numbers started to drop. Inpatient COVID-19 cases in Minnesota declined from 482 on May 31 to 403 on Friday.

Only 6% of those hospitalized patients needed intensive care, the lowest rate in the pandemic. Health officials believe high immunity levels from COVID-19 vaccinations and recent infections have lessened the severity of the latest wave along with available treatments.

Nearly half the ACTIV-6 ivermectin study participants had received COVID-19 vaccinations. Their recoveries were faster, but not by a significant margin. Patients with severe COVID-19 symptoms at the outset showed the most benefit from ivermectin compared with placebo pills, but the small number of them made their results subject to error or random chance.

"If that association in those with severe symptoms reappears (in the higher-dose trial) maybe it's real," said Boulware, but he was skeptical because there were only 90 patients in the trial who had severe symptoms at the time of enrollment.

The trial showed ivermectin to be relatively safe — side effects were rare and evenly split among the patients who took the drug or placebo.

Boulware has been a strong advocate for research of existing drugs, leading three trials that found that hydroxychloroquine didn't treat COVID-19. He criticized doctors who profited during the pandemic by promoting unsubstantiated treatments, but also the federal government for its slow support for research of existing drugs such as fluvoxamine, which is approved for depression.

"Those of us who were interested in testing existing medications received zero traction in applying for federal funding" during the pandemic's first year, he said. "I was zero for nine in (National Institutes of Health) grant applications."

Results are pending for the U's COVID-OUT trial, which used university funds and private grants to compare outcomes in COVID-19 patients who received fluvoxamine, ivermectin or metformin alone or in combinations. (Metformin usually treats diabetes and high blood sugar.) Enrollment was completed in January but the final study is awaiting formal publication in a medical journal.