COVID-19 Update: Ivermectin

Background: Throughout the COVID-19 pandemic, numerous therapeutic agents have been repurposed and applied empirically and within clinical trials. Prophylactic medications for COVID-19 could have a huge benefit, but studies to date haven’t panned out. Initially many therapeutic medications were used late in illness, and one of the criticisms of these negative studies was that the drugs were applied too late in the disease and therefore didn’t have any potential for benefit. There were also numerous studies showing associations of benefit, but subsequent randomized clinical trials have failed to prove effectiveness in reducing mortality (i.e. Remdesivir, hydroxychloroquine, lopinavir/ritonavir, colchicine, convalescent plasma, monoclonal antibody therapy).

Ivermectin is an anti-parasitic medication that has been the focus of speculation as an anti-viral, and anti-inflammatory medication against SARS-CoV-2 and COVID-19. In this post we will review some of the current evidence in using Ivermectin as a prophylactic and therapeutic agent in COVID-19.

Clinical Question: Does Ivermectin demonstrate efficacy in prophylaxis and treatment of COVID-19?

In Vitro Evidence [2]

  • Cells infected with SARS-CoV-2 RNA
  • Added Ivermectin or nothing (control) to cells and analyzed RT-PCR for replication of SARS-CoV-2 RNA at days 0 to 3
  • 24h = 93% reduction in viral RNA present
  • 48h = 99.8% reduction in viral RNA present
  • By 48hrs there was an ≈5000-fold reduction in viral RNA in Ivermectin treated cells compared to control samples
  • With a single dose of Ivermectin viral replication was controlled effectively eliminating all viral material by 48hrs
  • No toxicity observed at anytime
  • Proposed anti-viral mechanism of action

Studies You’ve Heard About But Determined to be Fraudulent

  • Largest and best RCT [3] on the use of Ivermectin (600 patients) from Egypt BUT…
    • Study retracted for ethical concerns of plagiarism and falsified data (Link is HERE)
  • Study out of Lebanon [11] in 100 asymptomatic patients retracted due to blocks of details of 11 patient’s data being copied and pasted repeatedly (Link is HERE)
  • MATH+ therapy touted by Pierre Kory also retracted due to flawed results (Link is HERE)

 Observational Data from Countries Using Prophylactic Ivermectin vs Those not Using Prophylactic Ivermectin [4]

  • Grouped countries into three different categories:
    • Include ivermectin in prophylaxis
    • Do not include ivermectin in prophylaxis
    • Do not do prophylaxis
  • Compared COVID-19 incidence between these three groups:

  • The fact that prophylaxis without ivermectin also showed a strong and statistically significant association with COVID-19 incidence suggests that other drugs could include additional candidates for the treatment and/or prevention of COVID-19
  • Conclusion:There seems to be an association rather than a causation of ivermectin use reducing COVID-19 incidence. However, we don’t know the rates of COVID-19 in these countries, crowding, testing availability, etc. There’s simply too much unknown information to make anything of this paper other than a hypothesis to study.

Evidence from Iraq [5]

  • Randomized controlled trial of 140 patients:
  • Ivermectin-Doxycycline reduced mean time to recovery from 17.9 to 10.61d in all recruited patients
    • In mild to moderate patients this reduction was from 13.66d to 6.34d
    • In severe patients this reduction was from 24d to 20d
    • This can have a tremendous effect on lowering the burden of disease and quickly freeing up hospital beds to other patients
  • Limitations:
    • Convenience sample: We have no idea how many patients total could have gotten treatment
    • Unclear what earlier means as there were no critical patients in the SOC arm
    • Non-blinded: Everyone knew what they were taking
    • Randomization method is flawed
    • Small study
    • No clear definition of recovery making this a subjective outcome that can bias the study
    • No idea if it’s the ivermectin or the doxycycline making the difference if you believe the difference
    • No information on patients to see if groups were balanced (i.e. demographics, underlying disease, etc.)
  • Conclusion:On the surface it seems Ivermectin with doxycycline reduced the time to recovery, percentage of patients who progress to more advanced stages of disease and reduced mortality. However, there were so many methodological issues I would not put any weight in these conclusions.

The ICON Study [7]

  • Retrospective observational cohort trial of consecutive patients hospitalized with COVID-19 from 4 hospitals in Florida
  • Reviewed charts of patients with COVID-19 treated with and without Ivermectin
  • This is the study that got everyone’s attention on Ivermectin as it was published in CHEST
  • Primary:All-cause in-hospital mortality
  • Results:
    • 280 patients (173 treated with Ivermectin and 107 without)
    • Patients received at least one dose of Ivermectin 200mcg/kg + standard care vs standard care alone
    • A second dose of 200mcg/kg of Ivermectin could be given on day 7 at the discretion of the treating clinician
    • Univariate analysis showed lower mortality in ivermectin group (15.0%vs 25.2%; OR 0.52; 95% CI 0.29 to 0.96; p = 0.03)
    • Mortality also lower in patients with severe pulmonary involvement (need for FiO2 ≥50%, NIV, or IMV)
      • 8% vs 80.7%; OR 0.15; 95% CI 0.05 to 0.47; p = 0.001
    • No difference in extubation rates or length of state
    • After multivariate adjustment for confounders, mortality difference remained significant (OR 0.27; 95% CI 0.09 to 0.80; p = 0.03)
    • Propensity matching was also used and found mortality to be significantly lower in ivermectin group (13.3% vs 24.5%; OR 0.47; 95% CI 0.22 to 0.99; p < 0.05) an 11.2% absolute risk reduction with a NNT of 8.9
  • Limitations:
    • Biggest limitation of this studyis that patients in the Ivermectin group got steroids far more commonly than those who didn’t:
      • Unmatched Cohort: 39.8% vs 19.6%
      • Matched Cohort: 25.5% vs 21.4%
    • More of the control group was enrolled in the 1stweeks of the study suggesting a timing bias. We get better at caring for a new disease as time goes on
  • Conclusion:According to the authors, Ivermectin treatment was associated with lower mortality during treatment of COVID-19, especially in patients with severe pulmonary involvement.  However more patients in the Ivermectin arm received corticosteroids than those who didn’t and the benefits seen in this trial may simply be due to this fact.

Summary of Clinical Evidence for Ivermectin Against COVID-19 [1]

Again, on the surface this looks promising, however going through the individual trials is essential, as the conclusions of any meta-analysis are only as good as the individual trials that go into it.  Many of these individual trials have methodological flaws that limit the utility of this analysis.

Poorly Done Trial + Poorly Done Trial + Poorly Done Trial = Poor Conclusion

Evidence from Spain [8]

What They Did: 

  • Pilot, randomized, double-blind, single-center, parallel-arm, superiority placebo-controlled trial performed in Spain
  • Evaluating single dose of ivermectin to reduce transmission of SARS-CoV-2 when administered early after disease onset
  • Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease presenting to the ED
  • All enrollments occurred within 72hrs of onset of fever or cough
  • Patients randomized 1:1 to receive:
    • Ivermectin 400mcg/kg single dose
    • Placebo single dose


  • Primary: Proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post treatment


  • 24 total patients
    • 100% had symptoms at recruitment
  • Ivermectin group had significantly lower viral loads at day 4 (3-fold lower) and day 7 (18-fold lower)
    • Confidence intervals crossed at all time points making this not statistically significant
  • Symptoms
    • Fewer days of any symptoms, however driven by anosmia/hyposmia (50% less) and cough (30% less)
    • No patients from either group progressed to severe disease
  • IgG Titers:
    • All patients in both groups seroconverted by day 21 post treatment
    • Lower IgG titers at day 21 post treatment in the ivermectin group (4.7 vs 7.5)
      • Not statistically significant
    • Safety:
      • No severe adverse events in either group
      • More dizziness and blurred vision with Ivermectin
    • Endpoint of negative PCR is not reflective of disease as patient can be fully recovered but still have enough viral material to be amplified by PCR (ie irrelevant viral material)
  • Bottom Line: Like many of the other studies reviewed on this post, the findings are interesting, however a RCT of 24 healthy patients, without comorbid disease, with no improvements in patient-oriented outcomes (i.e. mortality, progression of disease) does not justify early adoption of Ivermectin.

Evidence from India [9]

What They Did: 

  • Observational study of 118 healthcare providers in Bangladesh
  • Subjects divided into:
    • Experimental: Monthly Ivermectin 12mg x4months
    • Control: No treatment


  • Acquiring COVID-19


  • Healthcare workers working in COVID-19 isolation wards
  • Age 21 to 60 years
  • No treatment with any antiviral drugs


  • ≥60 years of age and <21 years of age
  • Pregnant women or lactating mothers
  • Chronic liver disease
  • Symptomatically ill


  • 118 healthcare workers
  • COVID-19 Diagnosis:
    • Experimental: 4/58 (6.9%)
    • Control: 44/60 (73.3%)
    • P <0.05


  • INTERESTING FACT:Ivermectin has a plasma half-life of ≈16 to 18hrs with time-length ranging from 4 to 12days. The reason this is interesting is that if Ivermectin is only given 1x/month you wouldn’t have effective drug in your system after 12 days. This makes a 1x/month dosing scheme pharmacologically irrelevant for the finding
  • A 70% conversion rate is ridiculously high. This makes me question how good PPE use and availability were during this trial

Bottom Line: Of all the studies reviewed in this post, this is the most promising. However it’s a single center study, observational and there are a number of factors that are unknown. Given the high conversion rate in the control group, it would be important to know what level of PPE was being used and if it was different between groups. Additionally, there was no patient oriented outcomes relegating the results of this study to promising and hypothesis generating requiring larger RCTs to confirm the results.

The EPIC Trial – RCT in Colombia [10]

Clinical Question: What is the effect of ivermectin on duration of symptoms in adults with mild COVID-19?

What They Did: 

  • Double-blind, randomized trial conducted at a single center in Colombia
  • Patients were identified by random sampling from the state’s health department electronic database
  • Patients randomized 1:1 to:
    • Ivermectin 300ug/kg per day x5d
    • Matching placebo per day x5d


  • Primary:Time to resolution of symptoms within 21d


  • 476 adult patients with mild disease included
    • 400 patients randomized in the primary analysis
    • Median age = 37 years
    • 79% did not have comorbid conditions at baseline
    • 398 (99.5%) completed the trial
  • No difference in adverse events or serious adverse events between groups


  • Young patient population without comorbid disease does not allow for extrapolation of results to older patients and/or patients with comorbid conditions
  • Up to August 26th, 2020 placebo was a mixture of 5% dextrose in saline and dextrose in distilled water. Due to potential for unblinding due to different taste and smell of ivermectin vs saline/dextrose placebo only 1 patient per household was included in the study to minimize chances of unblinding
  • Collected bottles at the end of study to certify adherence to the assigned regimen
  • Original primary outcome was defined as the time from randomization until worsening 2 points on the 8-category ordinal scale. Before the interim analysis, it became apparent that the pooled event rate of worsening by 2 points was substantially lower than the expected 18%, creating an unattainable sample size. Therefore, on Aug 31st, 2020 the primary outcome was changed to time from randomization to complete resolution of symptoms within 21d
  • On Oct. 20th, 2020 it was realized that a labeling error occurred between Sept 29thand Oct 15th, 2020 resulting in all patients receiving ivermectin and none receiving placebo during this time frame. Study blinding was not unmasked due to this error and these patients were excluded from the primary analysis
  • Authors used daily instead of intermittent dosing of ivermectin based on pharmacokinetic models showing higher lung concentrations with daily dosing
  • Although there was a numerically smaller group of patients in the ivermectin arm that required escalation of care vs placebo (2.0% vs 5.0%), this difference was not statistically significant and after removing 4 patients that were hospitalized within 3.25hrs after randomization this finding was further diminished
  • Additionally, ivermectin did not reduce ED visits or telephone consultations compared to placebo in this trial
  • Bottom Line: This randomized, double-blinded, placebo-controlled trial showed no benefit to the use of ivermectin compared to placebo in resolution of symptoms by 21 days. The methodology of this trial is certainly of better quality than previous trials, however there are some clear short comings with errors and potential for unblinding. Also, the relatively young and healthy study population included in this trial makes it difficult to extrapolate conclusions to older patient populations and/or patients with comorbid disease. We will just have to wait and see what future trials in different patient populations show.

Cochrane Review (Link is HERE)

Conclusion: “We found no evidence to support the use of ivermectin for treating or preventing COVID-19 infection, but the evidence base is limited.”


  • All of these trials discuss the efficacy of Ivermectin in the treatment of COVID-19 at various time points in illness, but very little was mentioned about safety
    • Due to its massive global use in low- and middle-income countries, the knowledge base establishing a high margin of safety and low rate of adverse effects is nearly unparalleled
    • Most common adverse events are mild and transient
    • Adverse effects are likely attributed to bodies inflammatory response and include itching, rash, swollen lymph nodes, joint pain, fever, and headache
    • In one trial of 17,877 patients treated with ivermectin 150mcg/kg for Loa loa in Cameroon. Only 20 patients (0.11%) developed serious reactions without neurological signs lasting for more than a week
  • The definition of insanity: Doing the same thing over and over again and expecting different results

Statement From Merck (Maker of Ivermectin) [Link is HERE]

Clinical Take Home Point:

  • There is no “High-quality” evidence showing that ivermectin plays a role in treatment of COVID19.Unless current ongoing RCTs show a benefit, ivermectin should only be used in the setting of a clinical study
  • Evidence for the use of Ivermectin is based on in vitro, prophylaxis, clinical, safety, and large-scale epidemiologic studies (heterogenous populations in multiple different settings) BUT…
  • Many of the trials thus far are methodologically flawed without enough information about baseline demographics, multiple primary outcomes, soft/subjective outcomes, convenience samples, and unclear definitions, just to name a few
  • Additionally, a valid concern in evaluating the literature is that many of the trials have not yet passed the peer review process and are in pre-print format
  • Although Ivermectin is cheap, readily available, with a fairly safe side effect profile, based on the evaluation of the literature above, at this time, Ivermectin should not be recommended outside of a clinical trial to ensure we get a true answer of effect
  • Ivermectin is interesting, there is certainly signal to evaluate further, but in our desire to want a treatment option, let’s not continue to do the same thing over and over again, as we saw play out with Hydroxychloroquine


  1. Kory P et al. Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19. FLCCC Alliance 2020. [Link is HERE]
  2. Caly L et al. The FDA-Approved Drug Ivermectin Inhibits the Replication of SARS-CoV-2 in Vitro. Antiviral Res 2020. PMID: 32251768
  3. Elgazzar A et al. Efficacy and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic. Research Square 2020 Pre-Print [Link is HERE]
  4. Hellwig MD et al. A COVID-19 Prophylaxis? Lower Incidence Associated with Prophylactic Administration of Ivermectin, International Journal of Antibcrobial Agents 2020. PMID: 33259913
  5. Hashim A et al. Controlled Randomized Clinical Trial on Using Ivermectin with Doxycycline for Treating COVID-19 Patients in Baghdad, Iraq. medRxiv PrePrint 2020 [Link is HERE]
  6. Gardon J et al. Serious Reactions After Mass Treatment of Onchocerciasis with Ivermectin in an Area Endemic for Loa Loa Infection. Lancet 1997. PMID: 9217715
  7. Rajter JC et al. Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with Coronavirus Disease 2019: The ICON Study. CHEST 2020. PMID: 33065103
  8. Chaccour C et al. The Effect of Early Treatment with Ivermectin on Viral Load, Symptoms and Humoral Response in Patients with Non-Severe COVID-19: A Pilot, Double-Blind, Placebo Controlled, Randomized Clinical Trial. Lancet 2021 [Link is HERE]
  9. Alam MT et al. Ivermectin as Pre-Exposure Prophylaxis for COVID-19 Among Healthcare Providers in a Selected Tertiary Hospital in Dhaka – An Observational Study. EJMED 2020. [Link is HERE]
  10. Lopez-Medina E et al. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults with Mild COVID-19: A Randomized Clinical Trial. JAMA 2021. PMID: 33662102
  11. Samaha AA et al. Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon. Viruses 2021. PMID: 34073401

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

Cite this article as: Salim Rezaie, "COVID-19 Update: Ivermectin", REBEL EM blog, December 16, 2020. Available at:
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Salim Rezaie

Emergency Physician at Greater San Antonio Emergency Physicians (GSEP)
Creator & Founder of REBEL EM

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62 thoughts on “COVID-19 Update: Ivermectin”

  1. i am puzzled why this post, on Dec. 17, makes the case that forward looking, placebo controlled, blinded studies have not been done and only three non-controlled studies are referenced. The material presented by Kory on December 8 referenced six other trial results that were forward looking, placebo controlled and single-blind. Those were the most compelling results, yet this post deprecates the effect by referring instead to less compelling data. Why is that?

    • Hello Lincoln,
      I have looked at all of the trials presented by Kory on Dec 8th…they all have methodological issues…I am happy to discuss any one of them individually but it would have been a broken record on this post…I actually have a graph at the bottom of the post that summarizes all the trials you are referring to…the point is you can’t just look at the summary. You have to look at all of the individual trials, which I have…none of them are well done but they are certainly interesting and warrant further study in a better done trial. Hope that helps.


  2. Your conclusion is not unlike those we’re hearing from CDC, NIH etc..

    State health agencies simply (and condescendingly) refer national agencies – incomplete or inadequate studies. There is no doubt that we (the ignorant masses) understand the obvious.

    However, if the potential (life-saving) benefit of Ivermectin is simply regarded as interesting to those with a scientific curiosity, believe me, there are hundreds of thousands of sick people/families HIGHLY interested in ANY chance to survive this virus.

    As the concerned national agencies and the medical academic community ponder absolutes and await trials they never order , the unwashed turnips are left to fend for ourselves and we will.

    People are informed to stay home if they test positive – only to darken the hospital door if they get really sick. That is too late as we are learning. If Ivermectin has a 50/50 chance of keeping us out of critical care and a <1% chance of reacting badly to the drug then for Pete's sake hand pills out like tictacs to covid+ people NOW. You will have tens of thousand of data samples in short order.

    I really see anything less at this point as medical malpractice.

  3. The money is in the vaccine. Ivermectin is to cheap. IT SHOULD BE AVAILABLE NOW OVER THE COUNTER AS IT IS IN NUMEROUS COUNTRIES.

    • I have read it…the ivermectin trials have severe methodological issues…I am not saying don’t use ivermectin…I am just saying use in a clinical trial…a well done RCT so we can know a true answer instead of giving things willy nilly and never knowing…This has become a broken record…hydroxychloroquine works…no it doesn’t…remdesivir works…no it doesn’t…convalescent plasma works…no it doesn’t. In our wanting a treatment so badly we rush to use things with bad science and only find later that these things don’t work and even worse…sometimes harm patients.


  4. “At its core, evidence-based medicine (EBM) incorporates clinical judgment, relevant scientific evidence, and patient values/preferences. Research and scientific evidence help inform care but should not dictate care of patients.”

    Note: The use of “Ivermectin” below would be as included in a standard of care.

    Is Ivermectin considered a safe drug if properly administered and not contra-indicated by existing prescription interaction?

    Would you give it to your 80 year old mother if she tested positive for covid but wasn’t quite ill enough for hospital admission?

    If she then started trending downward? Even when other active covid critical care professionals tell you it will save her life? Wow.

    Are you willing to bet other people’s lives that Ivermectin is indeed another HCQ – without evidence that it is (and some that it isn’t) ?

  5. @Kevin Dean, I couldn’t agree more. IFO know of several people who have taken Ivermectin plus corticosteroids who never saw a hospital and recovered completely. Several physicians i know personally or know of, routinely prescribe Ivermectin. If i tested positive i would not hesitate.

  6. curious as we look at ivermectin(Macrocyclic lactones) if the same can be said for Fenbendazole(Benzimidazoles)? I agree with some of the above, we live in a money grabbing world where the race for a vaccine is a race for patents and money.
    My deeper curiosity would be the method by which there is at least some evidence of Ivermectin working, is the mechanism the same as a Fenbendazole or similar medications? The main differences seem to be in the expedients in the medications to the best of my knowledge.

  7. I am a physician who practices outpatient primary care as well as inpatient hospital medicine.. I would not prescribe ivermectin for prophylaxis or to someone with mild symptoms, but I agree that based on the available evidence there is little downside to prescribing for the hospitalized patient who as at high risk of morbidity and mortality until higher quality RCCs are completed.

  8. No soy Médico, sin embargo alrededor de 50 conocidos, amigos y familiares han sanado en menos de 1 semana con ivermectina. Y 3 conocidos que no la usaron por desconfianza, fallecieron. Esta semana del 14 al 18 de diciembre 2020, 6 enfermos han ganado totalmente. Ahora tenemos casi 3 meses sin ningún fallecimiento en este municipio. ¿Será el uso masivo de la ivermectina por vos populi?

  9. Considering the current context of deaths and volume of positive data on Ivermectin, and low down side on negative effects, it is a smart decision to take it. Peru and Bolivia has it as national policy. Search a Nature article. Look statistics of new death, and new cases for them. Include Argentina and India. It is obvious that numbers are going down and there is no second wave, in spite of decreasing social distance.

  10. Regardless of the “trials”, you have medical doctors using both hydroxychloroquine and/or ivermectin. Even IF those didn’t work, why make it impossible for doctors to prescribe? Its all a sham and we are the sheep. There is no reason to come out and tell doctors they CANNOT prescribe safe drugs. Its all about that vaccine. Follow the money…….

  11. Salim Rezaie

    Thank you for your post I truly appreciate it. I have had several deaths in my immediate circle including great physician teachers. This is an epic tragedy. I am prescribing Ivermectin now to patients no matter where they are in the natural history of the disease. We never get to them at the initial stages because they all think they have the flu. Many have underlying health issues that they did not even know about until they got ill.

    I still prescribe HCQ despite all of the negative hype. The drug has been used since 1500 in one form or another, quinine, Chloroquine phosphate and now Hydroxychloroquine. The CDC’s own study proved it had prophylactic efficacy in vitro.
    None of my known lupus patients have had any issues on HCQ and there are numerous peer reviewed studies that support its use. No drug is perfect and neither are any studies. NO VACCINE IN USE HAS BEEN STUDIED EVER WITH A PROSPECTIVE RANDOMIZED STUDY YET THEY ARE GIVEN TO MILLIONS OF CHILDREN.

    We have to utilize every arrow in our quiver at this point. It and there is no going back now. I agree with many of the other post that the money is a pressing issue and care has taken a back seat

  12. It’s all about money. It’s unfortunate that the human race is profoundly retarded. It’s the blind leading the blind. There is absolutely nothing wrong in prescribing ivermectin but these bogus scientists want stupid evidence that they themselves are not going to conduct. They just sit and condemn other people’s efforts. Shame on them.

  13. @lincoln stoller Id say its because its sensationalism, bashing anything popular and controversial. My question is why is this very promising drug NOT getting the equal attention that vaccines are getting? Because there is no money behind it that is why I would say. Even if there are some issues as most things have, eg studies have flaws, sure-if there is a potential for this drug to be saving lives why is it not getting fast tracked. Could it be because its cheap and not a money spinner?

  14. To find funding; design an RCT; get it approved by ethics committee; enroll patients; complete and publish study!!! Wow. Too late for many. If NIH would simply remove their recommendation not to use ivermection, it would soon produce an observational trial (OT} on a national scale

  15. Salim Thank You. I found you last night. Today, My wife works for USPS she is 62. At work one her coworkers found out at work that she was exposed on Dec. 27. I’m 72 , a Vet. have COPD and a pacemaker. I called the VA today and they have no idea of a Ivermectin program. Will call my Doctors Monday. How can I get on a Ivermectin program? I’m am a rancher. Hope you can help me and my wife.

    • Hello Donald,
      This is a medical blog where health care professionals discuss current research. We do not give any medical advice on this website and if you are having issues, we strongly suggest you contact your physician for guidance.


  16. What precedent do you call upon to suggest treatments should not receive recommendations until large double blinded placebo controlled trials are done, and that studies with important limitations (“severe methodological flaws” is highly editorial) cannot guide treatments? 1A recommendations make up a small fraction of treatment recommendations. Most come from studies that you would call “highly methodologically problematic” or from “expert opinion only.” Disregarding a reproducible signal (there are multiple other studies you did not address), or “not putting any weight” to findings due to limitations, are really novel concepts, and a pandemic seems like an odd time to bust them out.

  17. Thank you Salim for another fantastic “FOAM journal club”.

    By reading some comments here and in twitter calling for emotion instead of reasoning in the ivermectin topic, I strongly recommend reading “”.

    Happy holidays!

    • Hey Bernardo,
      TY for the comment and the reminder for all of us to go based on facts and not emotions. I badly want something to work…I even hope it is Ivermectin as it is cheap and readily available. The problem with so many things during this pandemic is everyone jumps onto a bandwagon, only to find out what they were promoting either doesn’t work or worse yet caused harm. All I am saying is lets give it, but lets do it in a well done RCT so we can get a real answer instead of getting to the end of a pandemic and not really knowing what worked and what didn’t work. Happy Holidays to you too my friend.


  18. Hey Salim, congrats for another great post!
    You are right. It’s history repeating itself. What are we here for if not to learn from previous mistakes? Keep up your incredibly meritorious work.

    • TY so much Mariana,
      Try to be as objective as possible when reading and analyzing things. I really do want Ivermectin to work, but want it done right so we get a real answer. TY for reading and taking the time to leave a comment.


  19. “Zinc helps the body produce interferon when a virus is detected, and then dials down the immune response when the infection is cleared. Zinc also plays a role in maintaining epithelial tissue and improving mucin production, which can help prevent viruses from entering an animal’s body in the first place.”,body%20in%20the%20first%20place.
    (Like lost studies, these seem to ignore the function of HCQ and Ivermectin as the ionophore that aids zinc transport, and some say do nothing on their own without supplemental zinc

    • Hello Alberto,
      I have added the analysis of the trials you have sent me. Still no robust evidence…huge issues with both trials you sent me from a methodological perspective. Again, I hope this medication works, I want it to work, but we have to be careful making definitive statements when the evidence is just not there yet.


  20. Thank you for checking and including the studies. I agree with your analysis. The study from Bangladesh is the most promising, but it still has clear limitations. I still don’t know what to think about that strategy of giving the drug once per month. A low dose ever 24-48 hours would make more sense. But anyway, whatever works.

    Risk of bias is always there (though most of these studies have a higher than desired one), but it’s also true that bias can go both ways, so when it always goes one way it becomes statistically difficult that the results are due to biases. That was more or less my point about the feeling that the evidence adds up.

    Let’s wait and see. Other better trials are on the way, so I guess we’ll have better answers soon.

  21. Salim – I appreciate the fervor you express in pursuit of evidence-based medicine.
    We would all like more evidence.
    And this applies to most of the medicine we practice.

    I believe at this point the evidence of efficacy for ivermectin + low risk of harm + low cost is much more than adequate to compel its use on a widespread basis. And this is coming from a very strong proponent of evidence-based medicine. The studies are flawed, we get it. But flawed or not, the shear number of them and the persistently positive results (or trends for positive results) is just overwhelming. Numerous countries, authors, pt populations, doses, study types, etc. Doesn’t matter. The positive results just keep coming.

    The system, even in an uncoordinated/disjointed fashion, would continue to collect observational data going forward and controlled studies will come out as well. And there is a (small) possibility that the data could push the needle back towards no effect. At which point we would stop using it, much like we did (somewhat inappropriately) with hydroxychloroquine.

    But in the mean time, it is the right thing to do, morally/ethically/rationally/pragmatically. You cannot fairly apply such an excessively high standard of evidence to ivermectin but not to everything else you (and I) do for pts on a daily basis that have much less evidence of efficacy, higher risk of SEs, and higher cost. And the system can’t stop from endorsing its use at least on the level of other txs they have including remdesivir, IL-6 inh, JAK inhs, and the mabs.

    So, I think the best thing you can do with your platform is to start acknowledging that using ivermecitn for those at high risk of bad outcomes is currently the appropriate thing to do, but (yes, yes) in the mean time we will continue to collect data and await the results of ongoing studies. Do the right thing Salem, don’t yet your pride stand in the way. See the forest and not the trees, ya know.

    • Hello Philip,
      Appreciate your comments. No pride here…I even state in the post…I want a treatment…I hope this is it…I am not convinced…it still all boils down to methodology. The trials are hugely flawed. Lots of methodologically flawed studies put together still give us flawed conclusions. I hope I am proven wrong, want to be proven wrong, and am man enough to change my view if proven wrong. We all have to be careful pushing for something because of a need and a want to be able to do something that is not proven. I feel the same way about the mabs, remdesivir, convalescent plasma and so many other things that many are currently doing. The best thing we can continue to do on this platform, is critically appraise the evidence we do have and give balanced conclusions, which I feel we have done.


  22. Three friends were hiking a mountain trail when Dave slipped on a loose rock and slid over the edge of a 200 foot cliff. Luckily he managed to grab a small tree root 5 feet down.

    Johannes ran to the cliff edge and said “Hang on Dave I’ll throw you a rope!”.

    Frank said “Wait a minute this is a cheap box store rope – its not climbing approved.. Sorry Dave we can’t use this, the rope might break or you might even burn your hands.”.

    Johannes “It says the working load is 1000 lbs,- people use these all the time!”

    Frank “We don’t know for sure that its safe without UIAA testing.”

    Half a million Daves “AAAAAAaaaaaaaaa….”

    Fortunately I think the latest NIH position unties the hands of wary physicians’ ivermectin use. Now we just have to make them all aware of it.

  23. I’d stand somewhere in between: I prefer one good trial than 20 poor ones. Still, I really can’t ignore 20 poor ones in the current circumstances (and it’s all about risk/benefit, right?). I did find an interesting real-time meta-analyses website that has data from trials with different substances. On the probabilities of results due to bias, it says this:

    “The probability that an ineffective treatment generated results as positive as the 35 studies to date is estimated to be 1 in 34 billion (p = 0.000000000029).”

    Again, not that I specially like this sort of statistical analysis, but there it is anyway. If I had to say something with the current information, I’d say: “Use it. With care”. But I’d still keep waiting for better quality information, of course.

  24. Hello, just discovered this site and it’s amazing! I wanted to ask if you could recommend any books or other resources for biostatistics. Thank you.

  25. Doc, you need to call Dr. Hoan Pho (210-614-4000) here in San Antonio. He has been saving lives with Ivermectiin. Too many people needlessly dying while experts dawdle….get with it!

  26. Here is the thing. All experts are talking about a need for more high quality studies but no government in any of the first world countries (to the best of my knowledge) has committed any funds to such large scale studies, while spending at the same time billions of dollars trying to prop up failing economies. The first message about effectiveness of Ivermectin against the Covid-19 we heard almost a year ago. There should be by now a massive amount of high quality data from double blind, randomized trials with thousands of participants. There is however no interest amongst the governments in the low cost, highly effective solution which is the Ivermectin. Instead, all governments are prepared to spend billions of dollars on vaccines which are very questionable to say the list with their effectiveness and side effects. Are we just so stupid species or is there something else at play here? Who is running this world? Makes you think, doesn’t it?

  27. There are >20 RCT’s proving the effectiveness of ivermectin and of course JAMA publishes the one (colombia EPIC trial) that shows no benefit. Please read the meta analysis put on by other researchers, FLCCC is not the only one anymore, there is one in England as well called BIRD,, proving ivermectin’s overwhelming utility when given early in the disease and even more so when given prophylactically.

    We all know timing is super important for treating COVID-19, and during this trial (the colombia trial, published in JAMA) for all we know they could all be mostly 7 days out from positive testing and MISSED THE WINDOW OF OPPORTUNITY that Ivermectin works. I find it foolish they don’t give us the numbers of patients which were day 1, 2 or 3 and so on, out from positive testing. It must be given preferably with in the first onset of symptoms or even as prophylaxis, certainly prior to 5 days out, as the damage is already done and the virus has been already killed by the immune system.

  28. Thanks a lot Doc Salim for your post. Your assessments of the studies were very objective. We need this as medical professionals. I love the way you answer the comments – very humble and professional. Pls allow me to quote some of your comments in this post. Again, you’re doing a great job. God bless.

  29. Thank you for your rational analysis of the trials.

    It is interesting how some who have been promoting Ivermectin pointed to Peru where a correlation was seen between Ivermectin use and hospitalizations/deaths and to sub-saharan Africa with generally low counts and to India (until recently), but there seems to be silence regarding the recent rise in cases/hospitalizations/deaths in India (including in Uttar Pradesh where Ivermectin was used more heavily) and in Brazil where not only Ivermectin but Hydroxychloroquine is still being pushed. These aren’t RCTs (nor even formal observational trials) and there are many possible confounding factors, but if Ivermectin was so significant, one would think one would see it having a more positive effect in these countries/areas. More likely is that it either has no effect or a small effect, but only a properly done RCT can tell us with more confidence.

    • Appreciate you reading and leaving your thoughts. We always try to be objective and review the evidence we do have as what it is. I suspect there is a small effect, but as you stated…only a properly done RCT will be able to answer this.


  30. All i know is that Azithromycin could only temporarily ease my shortness of breath. After having long haul covid symptoms for 11 months, my shortness of breath and extreme fatigue disappeared a few days after taking my 1st capsule of IVM. It deserves more attention and support in data gathering is that is what is needed to make this available to everyone. It is proven safe and is meant for humans. Check the 2015 Nobel Peace Prize for Medicine on the work of 2 doctors on Ivermectin.

  31. While I may agree with the flaws and limitation that you have pointed out of the many studies that has been done in relation to ivermectin, unfortunately the same cannot be said to your conclusion. One may argue with the like of “Lots of methodologically flawed studies put together still give us flawed conclusions” but this does not necessarily a correct statement the whole time. Depending on the nature of the “flaws”, those study may actually strengthen one another. Moreover I do not understand how you come to the position of:

    1.”based on the evaluation of the literature above, at this time, Ivermectin should not be recommended outside of a clinical trial to ensure we get a true answer of effect”
    2. Ivermectin is interesting, there is certainly signal to evaluate further, but in our desire to want a treatment option, let’s not continue to do the same thing over and over again, as we saw play out with Hydroxychloroquine

    Point number 1 (why cant we give it to outside of clinical trial??) is clearly irrational given that we are in pandemic situation, people are getting severely sick and dies left and right. What other solution do you have for these people, just wait and die? wait for the vaccine? in some country there is huge waiting line to get the vaccine that goes to end of this year or even next year. Wait for a “flawed” proof large scale RCT study that you would probably approved, oversee, conducted, designed (No study is flawed proof by the way) that would be completed by end of the year (not to mention peer review process) and found out that yeah it does work, oops we just wasted last 6 month withholding these drug and patient are dying needlessly because of our irrational stand? And if it is proven to be false, then what is or where is the harm? does it make any difference?

    Point number 2 of “lets not continue to do the same thing over and over again as we saw with Hydroxychloroquine” – this is not a fair statement. There is huge differences between the safety profile and the quality and quantity of study of ivermectin v.s. hydroxychloroquine. So no…let us not compare it with hydroxychloroquine and confused ourselves by labelling / belittling it as doing the “same thing” over and over again. while we await for your golden standard study, lets use some common sense in or position with regard to ivermectin.

  32. Thanks for your interpretations, always a fan of your excellent work. In my practice I’ve had a couple patients ask about the FLCCC treatment algorithms which are using many things including Ivermectin, and I recently was forwarded a podcast found on their website. A guy named Bret Weinstein who is a evolutionary biologist and generally reputable interviews Dr. Pierre Kory, the CMO of the FLCCC on the topic and they have some very strong thoughts that go counter to traditional medicine. I’m not a research person and was curious your take on it.. their discussion definitely gives me pause. I’ve listened to Weinstein before and he seems very reasonable. I attached link to relevant podcast below. Cheers

  33. Completely agree with you Kevin. I would really appreciate Salim’s input on Dr Coreys arguments as I find them very compelling.

  34. Salim et al,

    So I don’t understand. Are we more interested in being purists with the data, or in improving patient outcomes? Can’t we study Ivermectin in RCT’s AND simultaneously recommend it’s use based on what we know to this point? Are these mutually exclusive?

    Seems crazy in a pandemic to avoid using a cheap, readily available and safe medication waiting for a ” true answer of effect”.
    Can’t we admit that the ” signal to evaluate further” is our academic position ( because we don’t want to ” repeat the same thing over and over) but that in clinical practice we need to use the best meds we have now?

    Ivermectin isn’t Hydroxychloroquine. There’s more data, a better safety profile, and more availability. This isn’t like TPA for CVA’s. It’s more like ASA before we had good data.

    Would you consider reaching out to Dr. Pierre Kory to dialogue on this issue? He’s very evidence based, and seems like a nice guy. His perspective deserves our attention. If he’s right, then we aren’t doing what best for patients.

    One of the most important issues ( that hasn’t been mentioned by you) is how much safer Ivermectin is than hydroxychloroquine.

    • Wray…no one on the REBEL EM site, including myself is saying it doesn’t work. All we are saying is that the evidence that supports its use is flawed. If you want to take it or prescribe it by all means…but this should not be made standard care with current evidence that we do have. Small, unblinded, non-RCT based studies is not what I would call the best for patient care. As I said in my post…I hope it works, I want it to work, but my interpretation of the evidence thus far hasn’t swayed me differently in my conclusions.


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