University of Kentucky Embraces Ivermectin & Other Experimental Medications in ‘Pick-the-Winner’ COVID-19 Trial

May 13, 2020 | Camostat, COVID-19, Hydroxychloroquine, Ivermectin, Leading Sites, News, SARS-CoV-2, Site Success, Site Watch, University of Kentucky

University of Kentucky Embraces Ivermectin & Other Experimental Medications in ‘Pick-the-Winner’ COVID-19 Trial

Clinical leaders from the University of Kentucky Markey Cancer Center College of Medicine and College of Pharmacy are now embarking on a novel path to investigate COVID-19 therapies. In a first in the United States, a major academic medical center has taken on Ivermectin as an experimental therapy targeting SARS-CoV-2, the virus that causes COVID-19—along with azithromycin and camostat mesylate. These drugs all could potentially inhibit replication of SARS-CoV-2. All three of these therapies will be tested alone or in combination with the antimalarial drug hydroxychloroquine. In a “pick-the-winner” trial, innovation and pragmatic experimentation meet clinical research collaboration in the Bluegrass State.

Ivermectin—Intriguing

TrialSite News has received hundreds of thousands of visits to our published material covering Ivermectin. From our first exposure of the University of Monash findings that the anti-parasitic medication can zap SARS-CoV-2 in a lab cell culture and the MedinCell research in France to clinical trials in Egypt and Iraq and of course the physician in Broward County using Ivermectin with dozens of patients—and apparently securing approval from the local health board along the way. Now a major research center embraces the potential—a widely available, cheap drug that could potentially help people fight off the deadly novel coronavirus.

Kentucky Derby Trial

In a trial akin to a Kentucky Derby, the University of Kentucky trial has a “pick-the-winner” design, which will allow UK researchers to rapidly understand what potential therapies appear to be effective, guiding patients to treatments that work and researchers to promising drugs that warrant further investigation.

Operating in a smart, sound and pragmatic manner, the team will scale up to a larger, more traditional placebo-control clinical trial using the most promising therapies with the best patient outcomes.

Dr. Susanne Arnold, a medical oncologist and associate director of clinical translation at the UK Markey Cancer Center who is co-leading the trial, noted, “We are pleased to be able to offer this clinical trial to patients with COVID-19 in Kentucky. 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.” She continued, “This rapid assessment means that the trial can quickly include and test new therapies as it identifies ones that are not effective.”

The Study

This Phase II study is reserved for patients both at home and in the hospital who have tested positive for SARS-CoV-2, or who have the symptoms but have not developed severe symptoms that would require progression to ICU care.  Patients must have at least one high-risk feature, including hypertension, diabetes, cancer, lung disease, have an underlying heart condition, or be over the age of 50. Outside of the hospital, clinical care and follow-up for research will be arranged in coordination with UK Healthcare’s Infectious Disease (ID) division under the direction of Dr. Alice Thornton. Researchers began consenting patients the first week of May and plan to enroll 240 patients over the course of the study. Patients with cases of COVID-19 who choose to enroll in the trial will be randomly assigned to one of four treatment groups: one group will receive hydroxychloroquine alone; a second group will receive hydroxychloroquine and azithromycin; a third group will receive hydroxychloroquine and ivermectin; and a fourth group will receive camostat mesylate. The study commences this month and runs ongoing until May 2021—as data is produced TrialSite News will track for updates.

The Investigational Drugs

Hydroxychloroquine and azithromycin are generic formulations long used to treat other conditions and their combined use has already shown promise in some early COVID-19 clinical trials. Hydroxychloroquine is used for the prevention and treatment of malaria as well as for autoimmune disorders including lupus and rheumatoid arthritis. In past research, it also showed some effectiveness against related coronaviral diseases MERS and SARS. Azithromycin is an antibiotic with an immunomodulatory effect that is used to treat many types of infections caused by bacteria, including respiratory, skin, ear and eye infections.

Ivermectin is an antiparasitic agent that also has activity in cellular models against a number of RNA viruses, including influenza, equine encephalitis and West Nile and appears to affect the entry of viral RNA into the cell nucleus. Note that for Ivermectin the dose will be based on weight (12 mg if less than 75kg and 15mg if over 75kg). Camostat mesylate is a serine inhibitor that has been used in Japan for 40 years to treat symptoms of chronic pancreatitis and postoperative esophageal reflux. Studies show that camostat mesylate can prevent cleavage of the spike protein in SARS-CoV-2, which is necessary for the virus to infect cells. The UK trial will be among the very first in the world to include this novel treatment.

“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,” said Dr. Zachary Porterfield, an infectious disease expert, virologist and assistant professor of medicine at UK who is co-leading the study with Arnold. “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 healthcare system.”

“The medications were selected by a multidisciplinary committee of medical experts from across the university. These were chosen as some of the most unique and promising initial trial study drugs that can be offered at the moment. Not only do they have some data to suggest they may work against COVID-19, these are all oral medications that are widely available and could have an effect worldwide,” said Porterfield.

UK Multi-Discipline Collaboration to Fight COVID-19

UK’s COVID-19 related research is coordinated by the COVID-19 Unified Research Experts (CURE) Alliance team, which is uniting UK medical researchers across disciplines in the fight against the novel coronavirus. The Alliance was launched and is supported by UK College of Medicine Dean Robert DiPaola and Vice President for Research Lisa Cassis. The CURE team is led by Rebecca Dutch, a virologist and chair of the department of molecular & cellular biochemistry.

A testament to the collaborative and interdisciplinary nature of the CURE Alliance, the design and implementation of this trial is truly indebted to the work of experts from across the university. Key insights in the trial have been provided by individuals like Dr. Elijah Kakani, a hospitalist physician who has been dedicated to developing the camostat mesylate arm of the trial, to Kip Guy, dean of the College of Pharmacy who has led a team of individuals in the evaluation of novel drug targets to be included in the trial, to Ken Campbell who has created a centralized biobank for management of blood and other samples from participants to help support crucial COVID-19 research and Jill Kolesar of the College of Pharmacy and Markey Cancer Center who provided critical insights on the viral testing platform used in the study.

Lead Research/Investigator

Susanne Arnold, MD, Associate Director of Clinical Translation

Zachary Porterfield, MD 

Elijah Kakani, MD 

In addition to principal investigators, Arnold and Porterfield, this study includes several co-investigators, including Dr. Zin Myint, Heidi Weiss, Donglin Yan, Dr. Therese Bocklage from the Markey Cancer Center; Dr. Aaron Hesselson from the College of Medicine; Jared Hammill and Frank Romanelli from the College of Pharmacy; and Scott Berry from the College of Engineering. Additional collaborators and consultants include Dr. Phil Kern, Dr. Robert DiPaola, Rebecca Dutch and Vivek Rangnekar.

Call to Action: The study commences this month and runs ongoing until May 2021—as data is produced TrialSite News will track for updates.

Source: EurekAlert!

5 Comments

  1. Paul E.

    This study titled “Usefulness of Ivermectin in COVID-19 Illness” by Amit N. Patel MD, MS. was released on April 19th 2020. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3580524

    However, there has been almost no media coverage of it or any further developments now for over 3 weeks. While the study is only a retrospective observational study it seems well designed. Here were my main takeaways (from a layman’s perspective):

    It was a retrospective study from 169 hospitals around the world. They reviewed over 68000 patients to select 1408 propensity matched patients. They divided them into two arms (704 each). The first was Ivermectin treatment group and the second was a control group with standard treatment (no Ivermectin). The main measured outcome was death. The result was the non-Ivermectin group had a 600% higher chance of death than the Ivermectin group. These results show a much higher efficacy than any other treatment that I’ve seen to date, including Remdesivir.

    Here are some additional notes about the trial that make the results even more impressive, IMHO:

    1. Ivermectin was dosed at only 150mcg/kg which is only 37.5% of the already proven safe dosing for other conditions.
    2. The Ivermectin group had more patients with CVD which is one of the highest risk factors with Covid-19 that leads to bad outcomes.
    3. The Ivermectin group had more severe disease at the start of the treatment as noted by the index of illness severity (qSOFA).
    4. The Ivermectin group had a larger percentage of black patients who statistically have shown worse outcomes with Covid-19.
    5. Ivermectin only costs .12 cents per patient (International wholesale price) versus the new standard of care, Remdesivir, which must be administered in a hospital at $5000/dose.
    6. Ivermectin can easily be prescribed outpatient via telemedicine to start the treatment early when it will be most effective. This is in contrast to Remdesivir which must be inpatient. The average time a patient presents at a hospital is 8days after onset of symptoms. As everyone knows, antivirals need to be administered as early as possible to inhibit the viral replication i.e. Tamiflu. The inpatient IV administration of Remdesivir makes this logistically impossible.

    Here is an excellent video that covers the Ivermectin study above and the mechanism of action: https://youtu.be/8Z1Oc4_99sk

    • TrialSite

      Dear Paul,
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  2. Dave S.

    I’m very excited about these trials. I would like to recommend that this study include Zinc supplements to the Hydroxychloroquine (HCQ) arm for a number of reasons.

    1.) One of the primary MOA of Hydroxychloroquine (especially in assisting the fight against RNA viruses like SARS-COV-2) is that it is a Zinc Ionophore, meaning it assists Zinc in passing our cell membranes. Zinc is known to disrupt many RNA viruses ability to replicate (disrupting the reverse transcriptase process). By inhibiting the viruses ability to replicate, our immune system can then gain ground on eradicating the virus more quickly and efficiently.

    2.) HCQ as a Zinc Ionophore relies on the body having enough Zinc to effect a positive MOA. It is well documented that most people borderline on Zinc deficiency from day to day. Thus, having more Zinc in the body is a key factor in promoting HCQ’s primary MOA.

    3.) Zinc is not stored in our bodies fat cells, etc. like some other vitamins and minerals, thus needs consistent replenishment through diet and supplementation. Compound this with the assumption that as people get sick (including contracting Covid-19), it is typical that food consumption is diminished, thus exasperating over the course of a few days to weeks the lowering of Zinc concentrations in the body. Supplementation of Zinc is a obvious answer to this challenge of keeping increased levels of Zinc in the body.

    For these reasons, please consider adding Zinc to the HCQ arm of the study in safe dosing amounts (i.e. .35mg-.5mg per lb of body weight, etc.). Not doing so can dramatically restrict the primary MOA of HCQ.

    Taking HCQ to combat an RNA virus like SARS-COV-2 without supplementing Zinc, would be akin to going on a long road trip in your car but starting out with only a quarter tank of gas…. you simply won’t get to your destination.

    Thank you for allowing me to comment and please consider adding Zinc to the HCQ arm of this trial if it’s not included currently.

      • TrialSite

        Dear Lou thanks for bringing this pre-publish document to our attention. We will read carefully.
        And thanks for visiting TrialSite News.
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