Dr. Paul Marik: Ivermectin Works and Should be Accepted for Large Observational Studies

Oct 28, 2020 | COVID-19, Ivermectin, News, Popular Posts

Dr. Paul Marik Ivermectin Works and Should be Accepted for Large Observational Studies

Dr. Paul Marik is a critical care physician who teaches medicine  at Eastern Virginia Medical School. Known for a vitamin C sepsis cocktail currently under clinical investigation, he recently posted an in depth YouTube lecture with a dire warning for Americans and the world. Disclosing that he has no affiliation with any commercial interests, the academic researcher and doctor suggests that, “the U.S. is in big trouble.” Now with over 9 million cases and 232,101 deaths according to most recent sources, Dr. Marik notes “the [COVID] cases are increasing at a remarkable rate.” Marik declares something must be done as Americans collectively move into winter, otherwise the outcomes could be “catastrophic.” He goes on to explain SARS-CoV-2 and the viral lifecycle as well as introduces the listener to possible ways that Ivermectin may inhibit SARS-CoV-2. He does a clinical study “meta-analysis” and pleads to health authorities to take this drug seriously. Although the National Institute of Health (NIH) Guidelines declares Ivermectin should only be used in clinical trials for COVID-19, they do now include the anti-parasite drug in the guidelines which wasn’t the case months ago. A growing tension mounts between research and regulatory authorities on the one side, and a rising number of independent-minded researchers and clinicians on the other side declaring sufficient data is in place for public funding in support of this economical and widely available generic drug.

Failed and Successful Rx

Interestingly, at 9:14 in his talk Dr. Marik presents a table titled: “Failed and Successful Rx for COVID-19 by Phase of Illness,” and includes a number of therapies that have been tested in COVID-19 patients. They include hydroxychloroquine, Remdesivir, Lopivnar-Ritonavir, Interferon Ab, Tocilizumab, convalescent plasma, and corticosteroids. Of these, Marik is doubtful except for corticosteroids which he acknowledges shows benefit (based on RECOVERY trial) at the “pulmonary/Inflammatory” stage of the illness. As to Remdesivir, he suggests there isn’t sufficient data to tell if there is any benefit at the pre-exposure/post-exposure and incubation phases of the illness. And the use of question marks indicates he at least wonders about the declared benefit  of “reduced time to recovery” during the symptomatic phase. He notes Remdesivir doesn’t reduce mortality. Remdesivir is the only drug approved by the U.S. Food and Drug Administration (FDA) for use against COVID-19. TrialSite, although critical of how Remdesivir was approved, certainly has accumulated significant data points that the drug helps. Convalescent plasma, for which the FDA controversially awarded an emergency use authorization (EUA), has questionable benefit, according to Marik. He suggests that the benefit of interferon alpha beta is uncertain at the pre-exposure/post-exposure incubation phase, while this therapy provides no benefit during the symptomatic phase and potentially harm during the pulmonary/inflammatory phase. The National Institutes of Health guidelines recommends against use of interferon Alpha Beta except for in clinical trials.

Some Hypotheses as to How Ivermectin may Inhibit SARS-CoV-2

The FDA approved drug Ivermectin was first demonstrated to inhibit SARS-CoV-2 by University of Monash, causing a 5000-fold reduction in viral RNA at 48 hours. The Australian researchers (Caly et al.) suggested that SARS-CoV-2 proteins, most importantly Orf6 and nucleocapsid proteins, need to bind to something to get into the human cell. This is accomplished by binding to importin proteins (alpha and beta), and this combined entity then penetrates the Nuclear Pore Complex allowing the SARS-CoV-2 proteins into the nucleus. Marik says that once these two proteins associated with COVID-19 enter the cell nucleus, “they cause havoc, cell arrest, they interfere with DNA transcription and  promote viral replication.” He notes Ivermectin binds to the importin complex and prevents SARS-CoV-2 proteins from binding to this importin mechanisms; therefore, the SARS-CoV-2 proteins cannot penetrate the nuclear core. Marik also introduces NF-kB and suggests some intriguing information. First, it was recently identified by a research team at Boston University and published in peer-reviewed Cell Stem Cell that SARS-CoV-2 causes major inflammatory trouble in the lungs via the activation of a biological pathway in the body known as NFkB (the k is pronounced “kappa”).

Marik suggests NFkB is an importin inflammatory-transcription vector that transcribes a host of inflammatory proteins. Made in the cytoplasm, it works in the nucleus and can penetrate the nuclear pore. Marik and the Monash hypothesis suggest that Ivermectin may prevent NFkB from binding to the key importins and hence inhibit entry into the nucleus. Marik introduces other possible benefits, such as docking to the SARS-CoV-2 “Spike receptor-binding Domain attached to ACE2.”  The Eastern Virginia Medical School professor and doctor goes on to review four clinical studies (also chronicled by TrialSite) including Mahmud, Rajter, Kahn, and Gorial and performs what he describes as a “meta-analysis” with mortality as an endpoint. He argues that the results indicate a “highly significant reduction in mortality.”

Critique of TrialSite Article

At 49:24 Dr. Marik refers to a TrialSite article titled, “India’s ICMR Excludes Ivermectin from National Guidelines for COVID-19: Not Sufficient Evidence via RCTs,” and he responds that there is in fact sufficient data via randomized studies, observational studies, and in vitro studies, as well as safety studies. He pleads: “What more do you need?” Dr. Marik suggests a major crisis is unfolding and calls for more observational studies in large groups of patients, even suggesting it could be unethical to conduct randomized studies with placebo given the number of deaths in this pandemic. TrialSite first and foremost is an independent and unbiased digital media. At present, we have no evidence that the Indian ICMR study was wrong based on their own internal decision making policies. There does appear to be a split in India between the national authorities and at least some state’s treatment guidelines that accept Ivermectin, however. Moreover, the National Institutes of Health (NIH) is clear about their recommended guidelines for Ivermectin—it can only be used in a clinical trial. TrialSite has been on the record numerous times arguing that an Ivermectin-based study should be funded by the NIH, and in fact one of our founders sent an email to Dr. Francis Collins recommending that NIH consider funding a clinical trial led by the physician/research authors of the ICON study—recently published in Chest.

Lead Researcher/investigator

Paul Marik, MD, Professor, Internal Medicine

Call to Action: Send us your comments. What are your thoughts on this topic?

Source: YouTube

18 Comments

  1. robin d gill

    Your critique notes: “There does appear to be a split in India between the national authorities and at least some state’s treatment guidelines that accept Ivermectin ~”

    “Some state’s treatment guidelines” is hardly sufficient qualification for India’s largest state w/ 210 million people that went all out with Ivermectin with results that more than back up Marik’s (or Borody’s) conclusion that Ivermectin can literally save us. Here is my layman’s way of summarizing

    Uttar Pradesh, an Indian state pop 210m recently ravaged by COVID-19, now boasts just 30 deaths/day! The US w/ just 1/3 more pop suffer 750 deaths/day. 25x more! WHY? They use Ivermectin right.

    And here a graphic posted by Chamie
    https://twitter.com/jjchamie/status/1320746434422067201/photo/1

    • TrialSite

      Dear Robin,
      We cannot disagree with you. If Uttar Pradesh were a nation it would be the 7th most populous in the world and although we haven’t substantiated the most recent statistics, in a couple discussions with local doctors we have heard anecdotally that results are there. And yes at this point we are struggling with a very different metric in the U.S.
      But one must ask the question why can’t such a big, influential and important Indian state, with proof in hand, convince the ICMR?
      Regards,
      Publisher

  2. jim goodyear

    Thank you Trialsite and Dr. Marik for this effort. I have read a lot of information about Ivermectin especially combining it with Doxycycline, Zinc, Vitamin B and D3 as prescribed by Dr. Thomas Borody of Australia. According to many studies around the world hundreds of thousands of people have been “cured” using this therapeutic. It has also proved to be a highly effective prevention. Someone needs to convince POTUS of this. He has the most power of anyone on the planet of disregarding the clout of big pharma and greed and stopping this pandemic.

    It will take years for a reliable vaccine to be developed and given the fact that the virus mutates, a specific vaccine for each variant will be needed. This may well be impossible.

  3. Paul Elkins

    Dr. Marik did a fantastic job reviewing the growing body of evidence supporting Ivermectin’s efficacy in Covid-19. We can’t forget that while the global health bodies (WHO) were issuing strong warnings against the use of systemic steroids Dr. Marik developed his now famous MATH+ Protocol with corticosteroids as the main pillar. If the world would have followed his lead rather than listening to the WHO’s incorrect warning regarding steroids hundreds of thousands of lives would have been saved. This became clear to the world only after many months later when the RECOVERY Trial proved systemic steroids resulted in a 35% reduction in mortality in critical cases.
    Dr. Marik’s open minded approach to adopt any therapeutic using a risk vs reward evaluation is what’s desperately needed during a rapidly evolving pandemic. It’s unconscionable that the NIH hasn’t funded an RCT many months ago on Ivermectin (and other promising repurposed, safe therapeutics). It’s extremely troubling how the NIH was very quick to use our tax dollars to fund Giliad’s Remdesivir RCT with $23M, change the primary endpoint, and obtain an FDA EUA on very questionable data. How was that funding appropriated so quickly? Did it have anything to do with the fact that 7 of the advisors on the NIH’s Covid-19 Treatment Guidelines Panel have disclosed financial ties to Gilead (the manufacturer of Remdesivir)? Also very concerning is that only days after the large international WHO SOLIDARITY Trial showed there was NO benefit in Remdesivir the FDA issued full approval. https://www.covid19treatmentguidelines.nih.gov/panel-financial-disclosure/
    Early intervention is imperative to prevent the disease progression and avoid the worst outcomes. Not nearly enough outpatient providers are actually treating this disease. Dr. Marik’s review of the compelling evidence for Ivermectin and its excellent safety profile provides the data for all outpatient providers to prescribe Ivermectin for Covid-19 off label if they feel it’s in the best interest of their patient. These decisions should be left in the hands of the trained physicians who deliver care to their patients.

    Dr. Marik’s video review: https://youtu.be/pU6nW97eQIU

  4. Uday Bose

    What should be the dose of Ivermectin and combination drugs like doxycycline, zinc etc ?

    • Paul Elkins

      Hi Uday, the most common dosing is:

      Ivermectin 200mcg/kg single dose
      Doxycycline 100 mg BID for 10days
      Zinc 50-75mg elemental during symptoms

      However, the optimal dosing for Ivermectin in Covid-19 is still being elucidated. There was an RCT out of Argentina that used 600mcg/kg for 3 consecutive days with excellent results. There are two currently running trials using up to 1200mcg/kg for 5 days (no results yet). Ivermectin has an excellent safety profile.

      For reference here is a link to Dr. Marik’s MATH+ Protocol: https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf

  5. Saurabh Singh

    In India, Ivermectin is a standard of care, alongwith Azithromycin and high dose VitC plus zinc. In Uttar Pradesh there are government orders asking physicians to prescribe Ivermectin.
    The recommendation was made 3 months ago by a panel of 20 leading internists who were working with co d patients since March. They also strongly recommended testing it’s efficacy in clinical trials. That is perhaps why ICMR is playing it safe- they are a federal body and can afford to take the high ground. State governments are answerable to their citizens and are throwing everything at the disease. Hence the dichotomy.

  6. MR PETER F BELL

    Thank you Paul Marik, MD, Professor, Internal Medicine ! Especially for the table on how things other than ivermectin don’t work…especially Remdesivir which must be supported by a biggish
    I think the problem is that ivermectin is so readily available and has been around for so very long, and has been and is still being used so much, that it would be like setting up a trial on water to see if it actually quenches your thirst.
    Ivermectin has been used an estimated four and a half billion times… isn’t that classed as “tested”?
    In Australia it just needs a doctor’s prescription, it is there on the shelf at the local chemist.
    But our govt ignores it and lets the old folk die.
    I’m interested in Dr. Borody’s idea of using a half dose (6mg?) for the front-line workers.

  7. Jason K Milner

    This is cure. The United States government may come around and accept the obvious. Better to try as many approaches as possible.

  8. Elena

    If I understood well, Marik found it fit to attack your site?
    This man is hungry for attention. Shame.

    • TrialSite

      We suspect at the core he isn’t pleased with the news out of India. That the ICMR didn’t embrace ivermectin despite what is happening at the state level such as in the large state of Uttar Pradesh (accepted ivermectin). With seeming evidence out of what would be the world’s 7th largest nation, it’s frustrating for many in that it seems that economical and available repurposed therapies that are evidencing possible safety and efficacy are shunned. We are just the messengers as we must report on what is in fact going on. We support different perspectives and work hard to keep this an objective and unbiased media platform. This is critically important but also a challenge because some of the politics unfolding are difficult and not seemingly rationale. We appreciate your visit and support.
      Publisher

    • ML

      Elena, your low blow to Dr. Paul Marik was not necessary; there’s no reason at all to throw disdain onto Dr. Marik for any reason. He is simply trying to save lives and get the message out to as many people as possible. You’ve obviously completely misinterpreted this good man’s intentions. TrialSite News is also trying to be objective and they are. Dr. Marik is fed up with the needless death and dying. So should we all be.

  9. Jogi Abraham

    I think ivermectin 12 gram tab once in a week as prophylaxis and if positive 12 gram tab daily for 7 days
    Needs further clarification..thanks

  10. arnold brenner MD

    Dr Marik has published important work in which he treated septic shock patients with hydrocortisone, thiamine, and intravenously administered high dose vitamin C. Both Coronavirus and septic patients have extremely low vitamin C blood levels, requiring repeated large repeated doses of ascorbate to be normalized.
    Does Dr Marik have any comments as to using IV vitamin for corona virus, as is being done in Shanghai China and one hospital system in New York State? Should the use of effective doses of oral nutrients which are known to be required by humans to fight infection (Vit C, zinc, Vitamin D magnesium and others) be encouraged, or must we wait for prospective, randomized double blind placebo controlled studies with statistical analysis to use these modalities?

  11. Jack Wesson

    I presume as a lay person it is the zinc ionophore mechanism that gives Ivermectin and Hydroxychloroquine their efficacy in fighting the coronavirus/covid-19. Have there been any studies to test the efficacy in treating (or prophylacticly) this coronavirus by any zinc ionophores that are nonprescription and inexpensively available to the US public now, such as quercetin or quinine (i.e. boiled grapefruit rinds)?

  12. taxi24hs

    Here in Brazil we have a medical doctor, leading image diagnosis expert, dr Lucy Kerr, who leads a 570 medical doctors team. This team is treating patients with Iveremctin , both in prevention care and already sick patients. This team has developed protocols. I and my family are using Ivermectin. I recommend get informed about their work. Some people near my family got infected covid and got cured with ivermectin. Prevention protocol: 6 mg per 30 kg weight – 2 days each 15 days. I weight 80 kg, so I took 3 capsules one day and the next day, Repeating every 15 days. People that can NOT USE Ivermectin: pregnant, kids under 15 kg and under 5 years old, and people currently with meningitis. Infected covid patients may need other drugs, besides Ivermectin: antibiotics, vit c, d, anti- inflammatory etc.
    Dr Lucy Kerr alerts: covid can leave permanent side-effects even in covid cured patients

  13. taxi24hs

    Again, here in Brasil, two city mayors (Itajaí and Natal), who are also medical doctors, made avaliable Ivermectin to its citizens, at no cost. To get the drug, the person has to get registered in the health system. This data is shared with the local University. Imagine the value of this wealthy data (thousands of patients data) to present and future studies about the benefits od this drug

  14. Greg

    Haven’t seen much discussion of famotidine, the gave to President Trump as well. Or better known as Pepcid AC. Even back in February the Chinese had observed that those already taking it faired better.

    Any studies?
    They did give it to the president.