University of Minnesota is leading an important HCQ clinical trial, including collaboration with McGill University Montreal, University of Manitoba and University of Alberta. The initiative is called Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP) at ClinicalTrials.gov. Excerpts in italics with my bolds. H/T Don Monfort
- To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus.
- To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
The Intervention Drug is Hydroxychloroquine. 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days Other Name: Plaquenil
This is the April 22, 2020: Second Interim Analysis Update
On April 22, 2020, the independent Data and Safety Monitoring Board (DSMB) for the COVID-19 post-exposure prophylaxis trial has reviewed the cumulative safety data from 783 participants in the ongoing hydroxychloroquine prevention trial. The DSMB has identified no safety concerns or efficacy concerns at this time. We congratulate the study investigators on their enrollment thus far, and we will continue to provide oversight for the trial as specified in the DSMB charter.
Based on the event rate of COVID-19 illness observed in the control group, the sample size can be reduced by approximately one-third with approximately 200 more research participants needed to complete the trial to demonstrate conclusively whether or not there is a 50% reduction in symptomatic illness with a 5-day course of hydroxychloroquine after a high-risk exposure to someone with COIVD-19. The next interim analysis is scheduled for May 6, 2020. Ongoing U.S. enrollment is occurring at http://www.covidpep.umn.edu and in Canada at: http://www.covid-19research.ca
What Theory of the Disease Covid19 Suggests this Intervention?
A plain language explanation comes from WebMD by way of the Daily Star Bangladesh Chloroquine, zinc tested to treat COVID-19 infection
In the United States and Europe, a handful of clinical trials have begun to test ways to keep healthcare workers and other vulnerable people safe from coronavirus disease (COVID-19).
Most are testing drugs called chloroquine or hydroxychloroquine that have long been used to prevent and treat malaria, and also as a therapy against rheumatoid arthritis and lupus. The hope is that, given before infection or early in the course of the disease, the drugs will protect someone against infection and illness from the virus, or, if they do, will ensure that their case is mild. But whether these drugs will help, hurt or do nothing remains an open question.
The virus that causes COVID-19 uses a backdoor to enter the cell. As it enters, it is exposed to an acidic, vinegar-like environment, which is actually needed for the virus to get all the way inside. Hydroxychloroquine, metaphorically keeps the cap on the vinegar, Greene says, preventing acidification. Thus, there is a scientific rationale for how this drug might exert an antiviral effect.
Mahir Ozmen, a professor of surgery at the Istinye University, School of Medicine in Istanbul, Turkey, says he thinks the best way to use chloroquine is in combination with zinc and vitamins C and D. He is running a clinical trial, testing to see whether this combination protects health care workers and their immediate families – including his own.
Ozmen, who is collaborating with a chest medicine specialist, an intensive care physician, and two infectious disease experts, says he intended to include only 80 participants, but 98 quickly volunteered. He began in April providing prophylactic therapy, and expects to complete the trial by July.
Ozmen says, “Hydroxychloroquine helps the zinc get inside the infected cells to destroy the virus, and vitamins A and D support immune function”. He gives volunteers a low dose of hydroxychloroquine every 3 weeks, and a vitamin tablet every day – or every other day for people prone to kidney stones. At the end of the trial, each participant will be checked for antibodies to COVID-19, suggesting an infection, whether they realised it or not.
This kind of prophylaxis will give us the time to develop a vaccine that will offer protection to everyone.
In perhaps the fastest-moving, large prophylaxis trial, researchers at Duke University are leading a US$ 50 million collaboration across hundreds of American healthcare systems, which will test 15,000 volunteers. Half the health care workers will take hydroxychloroquine, and half a placebo. Other drugs could be added to the study if they prove promising for preventing or lessening infection, says Adrian Hernandez, the trial’s principle investigator.
In France, researchers are running a trial with 1,200 healthcare workers to test prophylactic use of hydroxychloroquine or a combination of two HIV drugs, Lopinavir and Ritonavir, which failed as a treatment in people with severe COVID-19 infections but may work as prevention. It is expected to take 6 months.
In a 40,000-person trial led by the University of Oxford in England, participants in Asia will receive chloroquine or a placebo, and in Europe, hydroxychloroquine or a placebo. That trial is expected to take a year.
Footnote: A more detailed hypothesis for testing is provided by Dr. Scholz and Dr. Derwand of Leukocare in Munich (PDF here). Excerpt:
Based on the evidence of therapeutic effects of CQ/HCQ, their possible pharmacological effect as zinc ionophores and possibly underestimated specific and unspecific antiviral effects of zinc, we hypothesize that the combination of CQ/HCQ with parenteral zinc in the treatment of hospitalized COVID-19 patients may help to improve clinical outcomes and to limit the COVID-19 fatality rates.
Due to the existing substantial evidence, we propose to amend current clinical trial designs to test this hypothesis in the treatment of hospitalized COVID-19 patients by including at least one treatment arm with oral CQ or HCQ in combination with zinc. However, because of the better clinical safety profile HCQ should be preferred. To avoid interindividual differences of oral absorption rates and because of possible gastrointestinal side effects of oral zinc supplementation, it is proposed to use parenteral zinc preparations which are approved and clinically already used.