December 16, 2020

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 did not show any 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, convalescent plasma, monoclonal antibody therapy).

Ivermectin is an interesting medication that had fallen off my radar until recently.  It is an anti-parasitic medication, with potential anti-viral, and anti-inflammatory properties 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

Evidence from Egypt [3]

  • RCT of 600 patients (400 symptomatic confirmed COVID-19 & 200 healthcare and household contacts)
    • Group 1: 100 pts with mild/moderate COVID-19 infection + 4d course of 400ug/kg Ivermectin qD (max dose 24mg) + standard of care
    • Group 2: 100 pts with mild/moderate COVID-19 infection + 400mg hydroxychloroquine BID x1d, then 200mg BID for 5d + standard of care
    • Group 3: 100 pts with severe COVID-19 + 4d course of 400ug/kg Ivermectin qD (max dose 24mg) + standard of care
    • Group 4: 100 pts with severe COVID-19 + 400mg hydroxychloroquine BID x1d, then 200mg BID for 5d + standard of care
    • Group 5: 100 healthcare and/or household contacts PPE + ivermectin 400mcg/kg x1 and repeated in 1 week
    • Group 6: 100 healthcare and/or household contacts PPE only
  • Excluded pregnant, lactating, and critical cases (respiratory failure requiring mechanical ventilation, presence of shock, other organ failure)
  • Mild Cases = Mild symptoms such as anosmia, loss of taste, fever, respiratory or GI tract symptoms
  • Moderate Cases = Symptoms such as fever, respiratory tract or GI symptoms + pneumonia manifestations on chest imaging
  • Severe Cases =
    • RR >30/min
    • O2 sat <93%
    • PaO2/FiO2 < 200
    • Lung infiltrates >50% of lung fields or rapid progression within 24 – 48hrs
    • Respiratory support (i.e. HFNC or NIV or IMV)
  • Primary Endpoint: Improvement in clinical/laboratory investigations and/or 2 consecutive negative PCR tests taken at least 48hours apart, and hospital LOS
  • Results:
    • In mild, moderate and severe COVID-19 patients there was improvement in lymphocyte count, CRP, ferritin, d-dimer and RT-PCR conversion days in Ivermectin group compared to hydroxychloroquine group after one week of treatment
    • Mortality:
      • Ivermectin Group 1: 0%
      • Hydroxychloroquine Group 2: 4%
      • Ivermectin Group 3: 2%
      • Hydroxychloroquine Group 4: 20%
    • Mean Hospital LOS:
      • Ivermectin Group 1: 5 +/- 1d
      • Hydroxychloroquine Group 2: 15 +/- 8d
      • Ivermectin Group 3: 6 +/- 1d
      • Hydroxychloroquine Group 4: 18 +/- 8d
    • Prevention of COVID-19 Infection in Healthcare or Household Contacts of COVID-19:
      • Ivermectin Group 5: 2%
      • No Ivermectin Group 6: 10%
    • Limitations:
      • Multiple primary endpoints with many being subjective/soft
      • Trial not registered at clinicaltrials.gov so can’t really check on what outcomes were originally set as primary outcomes and what was added or found through analysis
    • Conclusion: Ivermectin in addition to standard care was more effective in treatment and prophylaxis compared to hydroxychloroquine in addition to standard care according to the authors. Without a placebo arm, we do not know if ivermectin is superior to standard care alone.  Additionally, the methodology has concerning issues including multiple primary outcomes.

Evidence 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:
    • 70 COVID-19 patients (48 mild-moderate, 11 severe, and 11 critical patients) treated with 200ug/kg PO of ivermectin qD for 2 to 3 days + 100mg PO doxycycline BID for 5 to 10 days + standard of care
    • 70 COVID-19 patients (48 mild-moderate and 22 severe and zero critical patients) treated with standard of care alone
    • Mild to moderate disease = outpatients
    • Severe/Critical disease = inpatients
  • Results:

  • 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 study is 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 1st weeks 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

Discussion:

  • 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

  • ADDENDUM (12/21/2020):

    • I want to be clear about what I am saying in this post. I am not against using ivermectin but not sold on it based on the available data thus far…lots of issues that bias the results to favor ivermectin. Maybe it works or maybe it doesn’t, but I think the jury is still out at this point in time.
  • ADDENDUM (01/21/2021) – Two More Trials Sent My Way for Review

    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

    Outcomes:

    • Primary: Proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post treatment
    • Secondary:
      • Viral load at days 4, 7, 14, and 21 post treatment
      • Proportion of patients with symptoms (fever and cough) at days 4, 7, 14, and 21 post treatment
      • Proportion of patients progressing to severe disease or death during the trial
      • Proportion of patients with seroconversion at day 21 post treatment
      • Proportion of drug-related adverse events

    Inclusion:

    • Patients presenting to the ED
    • Symptoms compatible with COVID-19
    • No more than 72hrs of fever or cough
    • Positive PCR for SARS-CoV-2

    Exclusion:

    • Positive IgG against SARS-CoV-2
    • Comorbidities considered risk factors for severe disease
    • COVID-19 pneumonia at baseline

    Results:

    • 24 total patients
      • 100% had symptoms at recruitment
    • Proportion of patients with Detectable SARS-CoV-2 at Day 7 Post Treatment:
      • Ivermectin:
        • Gene N: 100%
        • Gene E: 91%
      • Placebo:
        • Gene N: 100%
        • Gene E: 100%
      • RR 0.92; 95% CI 0.77 – 1.09; p = 1.0
    • 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

    Strengths:

    • Asks a clinically relevant question
    • Randomized, double-blind, placebo-controlled trial
    • All patients recruited completed the trial
    • No difference in vital signs, inflammatory markers or blood counts between groups

    Limitations:

    • Small trial (n = 24 patients)
    • Surrogate soft outcomes without any patient oriented outcomes (i.e. mortality)
    • Placebo tablets did not match Ivermectin tablets which could lead to unblinding
    • Slow recruitment (24 patients over 10 weeks)
    • 94 patients assessed however many excluded due to not wanting to participate, or asymptomatic (70 patients excluded)
    • Trial too small to make any conclusions about adverse effects
    • Only included healthy patients with no comorbid disease

    Discussion:

    • Authors were looking for a 50% reduction in the proportion of positive SARS-CoV-2. This large reduction was due to the small size of the trial.
    • 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)

    Author Conclusion: “Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400mcg/kg dose of ivermectin within 72 hours of fever or cough onset there was no difference in the proportion of PCR positives.  There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials.”

    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

    Outcomes:

    • Acquiring COVID-19

    Inclusion:

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

    Exclusion:

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

    Results:

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

    Strengths:

    • Asks a clinically important question
    • Included healthcare workers which are at high risk of COVID-19 infection

    Limitations:

    • Observational not RCT, which means confounders could affect the results. For example, it is unclear what PPE was used during this study
    • Only subjects who became symptomatic were tested. It is unclear what these results would be if asymptomatic subjects were included (i.e. knowing infection rate is not clear from this data)
    • Excluded highest risk groups: age >60, liver disease, pregnant/lactating women

    Discussion:

    • 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

    Author Conclusion: “Ivermectin, an FDA-approved, safe, cheap and widely available drug, should be subjected to large-scale trials all over the world to ascertain its effectiveness as pre-exposure prophylaxis for COVID-19.”

    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.

Clinical Take Home Point:

  • 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

References:

  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]

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: https://rebelem.com/covid-19-update-ivermectin/.
The following two tabs change content below.

Salim Rezaie

Emergency Physician at Greater San Antonio Emergency Physicians (GSEP)
Creator & Founder of REBEL EM
42 Comments
  • Treatment and Management Research – COVID-19 Resources
    Posted at 10:23h, 17 December Reply

    […] REBEL EM Summary of the Evidence […]

  • Back to ivermectin, what about the evidence? – COVID-19 Questions and Answers
    Posted at 09:12h, 18 December Reply

    […] REBEL-EM, provided a really thorough review of several key ivermectin studies in its post of 12/16, COVID-19 Update: Ivermectin, concluding “Ivermectin is interesting, there is certainly signal to evaluate further, but in […]

  • lincoln stoller
    Posted at 03:15h, 19 December Reply

    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?

    • Salim Rezaie
      Posted at 05:17h, 19 December Reply

      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.

      Salim

  • Kevin Dean
    Posted at 12:53h, 19 December Reply

    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.

  • tom s brown
    Posted at 18:27h, 19 December Reply

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

    • Salim Rezaie
      Posted at 07:10h, 20 December Reply

      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.

      Salim

  • Kevin Dean
    Posted at 00:00h, 21 December Reply

    “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) ?

  • Rafael Villafane
    Posted at 12:46h, 21 December Reply

    @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.

  • Korey Sternard
    Posted at 16:32h, 21 December Reply

    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.

  • chad osborne
    Posted at 19:43h, 21 December Reply

    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.

  • Américo Guerra
    Posted at 23:33h, 21 December Reply

    Ok look at https://www.youtube.com/watch?v=flZWI3dbXRE and tell me what’s your bias or agenda!

  • José AtIlano Cruz Lopez
    Posted at 08:12h, 22 December Reply

    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?

  • EDUARDO GIULIANI
    Posted at 09:24h, 24 December Reply

    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.

  • Chuck V
    Posted at 08:52h, 25 December Reply

    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…….

  • Ishtiaq Bashir
    Posted at 08:21h, 28 December Reply

    Interesting but needs more review.

  • David P
    Posted at 03:53h, 30 December Reply

    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

  • Felix Moyo Edonmi
    Posted at 10:18h, 30 December Reply

    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.

  • Tim Cook
    Posted at 02:25h, 31 December Reply

    Can you offer a critique of the forward looking, placebo controlled, blinded studies that Dr. Kory presented?

    • Salim Rezaie
      Posted at 08:05h, 31 December Reply

      Happy to…send over the links and happy to go through them one by one.

      Salim

  • Juan
    Posted at 12:12h, 01 January Reply

    @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?

  • robert corliss
    Posted at 13:51h, 02 January Reply

    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

  • Donald William Ringwood
    Posted at 19:05h, 02 January Reply

    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.

    • Salim Rezaie
      Posted at 21:35h, 02 January Reply

      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.

      Salim

  • Eric Osgood
    Posted at 10:08h, 03 January Reply

    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.

  • Bernardo Vidal Pimentel
    Posted at 12:44h, 03 January Reply

    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 “https://emj.bmj.com/content/37/9/572”.

    Happy holidays!

    • Salim Rezaie
      Posted at 14:00h, 03 January Reply

      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.

      Salim

  • Mariana Barosa
    Posted at 16:04h, 03 January Reply

    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.
    Mariana

    • Salim Rezaie
      Posted at 16:06h, 03 January Reply

      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.

      Salim

  • Ivermectin - WeeksMD
    Posted at 21:40h, 05 January Reply

    […] FOR MORE INFO on IVERMECTIN – see this link https://rebelem.com/covid-19-update-ivermectin/ […]

  • Kevin Dean
    Posted at 12:21h, 06 January Reply

    Meta-analysis from UK:

    Tess Lawrie MBBCh, PhD;
    E-BMC Ltd, Office 305, Northgate House, Upper Borough Walls, Bath, United Kingdom
    Email: info@e-bmc.co.uk
    Website: http://www.e-bmc.co.uk:
    ORCID iD 0000-0002-5500-8590
    https://www.researchgate.net/profile/Theresa_Lawrie

    https://b3d2650e-e929-4448-a527-4eeb59304c7f.filesusr.com/ugd/593c4f_8cb655bd21b1448ba6cf1f4c59f0d73d.pdf

  • Enginer01
    Posted at 07:58h, 13 January Reply

    “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.”
    https://essentialfeed.zinpro.com/2020/06/trace-minerals-help-prevent-virus-replication-boosts-immune-response-to-viral-infections/#:~:text=Zinc%20helps%20the%20body%20produce,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

  • Kevin Dean
    Posted at 10:36h, 17 January Reply

    NIH has an update.
    https://www.covid19treatmentguidelines.nih.gov/statement-on-ivermectin/

    Neither for or against the use of Ivermectin for covid 19.

  • Alberto
    Posted at 19:27h, 19 January Reply

    Yes, none of the evidence is definitive, but it keeps adding up (or so it seems to me). Here others I think not considered in the post:

    https://doi.org/10.1016/j.eclinm.2020.100720

    https://doi.org/10.24018/ejmed.2020.2.6.599

    • Salim Rezaie
      Posted at 15:54h, 21 January Reply

      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.

      Salim

  • Alberto
    Posted at 20:00h, 21 January Reply

    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.

  • philip willsie
    Posted at 22:05h, 21 January Reply

    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.

    • Salim Rezaie
      Posted at 22:14h, 21 January Reply

      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.

      Salim

  • Kevin Dean
    Posted at 00:01h, 22 January Reply

    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.

  • Alberto
    Posted at 13:47h, 22 January Reply

    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).”

    https://ivmmeta.com/

    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.

Post A Comment

Time limit is exhausted. Please reload CAPTCHA.

0