Database of all ivermectin COVID-19 studies. 105
studies, 68 peer reviewed, 60 with
results comparing treatment and control groups. Submit
updates/corrections below. FLCCC
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Covid Analysis (Preprint) (meta analysis)
meta-analysis v103
Ivermectin for COVID-19: real-time meta analysis of 60 studies
Details
• Meta analysis using the most serious outcome reported shows 74% and 85% improvement for early treatment and prophylaxis (RR 0.26 [0.16-0.43] and 0.15 [0.08-0.25]), with similar res..
• The probability that an ineffective treatment generated results as positive as the 60 studies to date is estimated to be 1 in 193 billion (p = 0.0000000000052).• Heterogeneity arises from many factors including treatment delay, population, effect measured, variants, and regimens. Associations identified in pooled analysis are valid and underestimate the effect size for the optimal case. Heterogeneity is low in specific cases, for example early treatment mortality.• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 30% of ivermectin studies show zero events in the treatment arm.• Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. All practical, effective, and safe means should be used. Those denying the efficacy of treatments share responsibility for the increased risk of COVID-19 becoming endemic; and the increased mortality, morbidity, and collateral damage.• Administration with food, often not specified, may significantly increase plasma and tissue concentration.• The evidence base is much larger and has much lower conflict of interest than typically used to approve drugs.• All data to reproduce this paper and sources are in the appendix. See [Bryant, Hariyanto, Hill, Kory, Lawrie, Nardelli] for other meta analyses, all with similar results confirming effectiveness.
Santin et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100924 (Review) (Peer Reviewed)
review
Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19
Details
Review concluding that the evidence supports worldwide use of ivermectin for COVID-10, complementary to immunization. Authors note that it is likely non-epitope specific, possibly retaining efficacy with new viral strains. They note that ..
Santin et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100924 (Review) (Peer Reviewed)
Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19
Review concluding that the evidence supports worldwide use of ivermectin for COVID-10, complementary to immunization. Authors note that it is likely non-epitope specific, possibly retaining efficacy with new viral strains. They note that ivermectin has been safely used with 3.7 billion doses since 1987, is well tolerated even at much greater than standard doses, and has been used without serious AEs in high-dose COVID-19 treatment studies.
Santin et al., 8/3/2021, peer-reviewed, 5 authors.
Popp et al., Cochrane Database of Systematic Reviews, doi:10.1002/14651858.CD015017.pub2 (Preprint)
meta-analysis
Ivermectin for preventing and treating COVID‐19
Details
Outdated very biased retrospective meta analysis cherry-picking a small subset of studies, with a majority of results based on only 1 or 2 studies, showing positive (non-statistically significant) results for 10 of 11 primary outcomes acr..
Popp et al., Cochrane Database of Systematic Reviews, doi:10.1002/14651858.CD015017.pub2 (Preprint)
Ivermectin for preventing and treating COVID‐19
Outdated very biased retrospective meta analysis cherry-picking a small subset of studies, with a majority of results based on only 1 or 2 studies, showing positive (non-statistically significant) results for 10 of 11 primary outcomes across a total of 13 studies.This analysis splits up studies in order to dilute the effects and avoid statistical significance. However, we can consider the probability of 10 of 11 positive effects occurring due to chance for an ineffective treatment, which is very unlikely (p = 0.006), indicating efficacy.The study is entirely retrospective in the current version. The protocol is dated April 20, 2021, and the most recent study included is from March 9, 2021. The protocol was modified after publication in order to include a close to null result (Gonzalez et al. "patients discharged without respiratory deterioration or death at 28 days"), so the current protocol is dated July 28, 2021. The analysis may become partly prospective in the future if the authors do not continue to change the protocol.Authors excluded many studies by requiring results at a specific time, for example mortality, ventilation, etc. required results at exactly 28 days. Authors excluded all prophylaxis studies by requiring results at exactly 14 days.Studies comparing with other medications were excluded, however these studies confirm efficacy of ivermectin. The only case where they could overstate the efficacy of ivermectin is if the other medication was harmful. There is some evidence of this for excessive dosage/very late stage use, however that does not apply to any of the studies here.Studies using combined treatment were excluded, even when it is known that the other components have little or no effect. 3 of 4 RCTs with combined treatment use doxycycline in addition [1].Other studies were excluded by requiring PCR confirmation.Cochrane was reputable in the past, but is now controlled by pharmaceutical interests. For example, see the news related to the expulsion of founder Dr. Gøtzsche and the associated mass resignation of board members in protest [2]. For another example of Cochrane bias see [3].Authors report funding from the German Federal Ministry of Education and Research, which may be influenced by [4].Bias due to funding is ignored for both analyzed studies and Cochrane. For Cochrane funders see: [5, 6].The BiRD group gave the following early comment: "Yesterday’s Cochrane review surprisingly doesn’t take a pragmatic approach comparing ivermectin versus no ivermectin, like in the majority of other existing reviews. It uses a granular approach similar to WHO’s and the flawed Roman et al paper, splitting studies up and thereby diluting effects. Consequently, the uncertain conclusions add nothing to the evidence base. A further obfuscation of the evidence on ivermectin and an example of research waste. Funding conflicts of interests of the authors and of the journal concerned should be examined."
Ontai et al., medRxiv, doi:10.1101/2021.07.21.21260223 (Preprint)
Early multidrug treatment of SARS-CoV-2 (COVID-19) and decreased case fatality rates in Honduras
Details
Report on the nationwide implementation of multi-drug COVID-19 inpatient and outpatient treatment protocols in Honduras, showing a case fatality rate decrease from 9.33% to 2.97%. No decrease was seen in Mexico, a similar Latin American c..
Ontai et al., medRxiv, doi:10.1101/2021.07.21.21260223 (Preprint)
Early multidrug treatment of SARS-CoV-2 (COVID-19) and decreased case fatality rates in Honduras
Report on the nationwide implementation of multi-drug COVID-19 inpatient and outpatient treatment protocols in Honduras, showing a case fatality rate decrease from 9.33% to 2.97%. No decrease was seen in Mexico, a similar Latin American country that did not introduce multi-drug treatment protocols at that time. Decreases in COVID-19 case fatality rates in Honduras were associated with both the initial publication of the protocol and a subsequent outreach program. Both inpatient and outpatient protocols include ivermectin as one component.
FLCCC Alliance and British Ivermectin Recommendation Development Group (News)
news
Joint Statement of the FLCCC Alliance and British Ivermectin Recommendation Development Group on Retraction of Early Research on Ivermectin
Details
News release noting that ivermectin remains effective after excluding Elgazzar et al. Given the large magnitude effects and 61 studies, excluding one study with ~3% of patients does not significantly change the evidence base.
FLCCC Alliance and British Ivermectin Recommendation Development Group (News)
Joint Statement of the FLCCC Alliance and British Ivermectin Recommendation Development Group on Retraction of Early Research on Ivermectin
News release noting that ivermectin remains effective after excluding Elgazzar et al. Given the large magnitude effects and 61 studies, excluding one study with ~3% of patients does not significantly change the evidence base.
Neil et al., ResearchGate, doi:0.13140/RG.2.2.31800.88323 (Preprint)
meta-analysis
Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease
Details
Bayesian analysis of a subset of ivermectin trial data concluding that there is overwhelming evidence to support a causal link between ivermectin, COVID-19 severity, and mortality.
Neil et al., ResearchGate, doi:0.13140/RG.2.2.31800.88323 (Preprint)
Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease
Bayesian analysis of a subset of ivermectin trial data concluding that there is overwhelming evidence to support a causal link between ivermectin, COVID-19 severity, and mortality.
Hazan et al., medRxiv, doi:10.1101/2021.07.06.21259924 (Preprint)
death, ↓85.9%, p=0.04
Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients
Details
Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatme..
Hazan et al., medRxiv, doi:10.1101/2021.07.06.21259924 (Preprint)
Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients
Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatment. Two patients declined treatment and both died. This study uses a synthetic control arm.
risk of death, 85.9% lower, RR 0.14, p = 0.04, continuity correction due to zero event.
risk of hospitalization, 93.3% lower, RR 0.07, p = 0.001, continuity correction due to zero event.
Hazan et al., 7/7/2021, retrospective, USA, North America, preprint, 7 authors, dosage 12mg days 1, 4, 8, this trial uses multiple treatments in the treatment arm (combined with doxycycline, zinc, vitamin D, vitamin C) - results of individual treatments may vary.
Vallejos et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06348-5 (Peer Reviewed)
death, ↑33.5%, p=0.70
Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial
Details
RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, the trial is underpowered. The trial primarily includes low-risk patients that recover quickly without tr..
Vallejos et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06348-5 (Peer Reviewed)
Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial
RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, the trial is underpowered. The trial primarily includes low-risk patients that recover quickly without treatment, leaving minimal room for improvement with treatment. 74 patients had symptoms for >= 7 days and more than 25% of patients were hospitalized within 1 day (Figure S2). Among the 7 patients requiring ventilation, authors note that the earlier requirement in the ivermectin group may be due to those patients having higher severity at baseline. However, authors know the answer to this - it is unclear why it is not reported. There were more adverse events in the placebo group than the ivermectin group, suggesting a possible issue with dispensing or non-trial medication usage.Authors pre-specify multivariate analysis but do not present it, claiming "no significant differences in the univariate analysis", however multivariate analysis could significantly change the results. Consider for example if just a few extra patients in the ivermectin group were in severe condition based on baseline SpO2. The lower mean SpO2 in the ivermectin group, and the shorter time to ventilation, are consistent with this being the case. Additionally, there are 14% more male patients in the ivermectin group.An extremely large percentage of patients (55%) were excluded based on ivermectin use in the last 7 days. However, ivermectin may retain efficacy much longer (for example antiparasitic activity may persist for months [1]). A significant number of patients may also misrepresent their prior and future usage - the population is clearly aware of ivermectin, and patients with progressing disease may be motivated to take it, predicting that they are in the control group.There were no serious adverse events. NCT04529525.
Turkia, M., ResearchGate, doi:10.13140/RG.2.2.16973.36326 (Review) (Preprint)
review
A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021]
Details
An extension of the ivermectin timeline covering April - June 2021, including WHO's role and funding, Gavi, COVAX, Trusted News Initiative, International Fact-Checking Network, the role of private philantrophy, Frontiers, comparison to th..
Turkia, M., ResearchGate, doi:10.13140/RG.2.2.16973.36326 (Review) (Preprint)
A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021]
An extension of the ivermectin timeline covering April - June 2021, including WHO's role and funding, Gavi, COVAX, Trusted News Initiative, International Fact-Checking Network, the role of private philantrophy, Frontiers, comparison to the H1N1 pandemic, new treatment protocols, and causal modeling.
Roman et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab591 (preprint 5/25/21) (Peer Reviewed) (meta analysis)
meta-analysis
Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials
Details
Severely flawed meta analysis. An open letter signed by 40 physicians detailing errors and flaws, and requesting retraction, can be found at [1]. See also [2].
The authors state that they have no conflicts of interest on medRxiv, however..
Roman et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab591 (preprint 5/25/21) (Peer Reviewed) (meta analysis)
Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials
Severely flawed meta analysis. An open letter signed by 40 physicians detailing errors and flaws, and requesting retraction, can be found at [1]. See also [2].The authors state that they have no conflicts of interest on medRxiv, however Dr. Pasupuleti’s affiliation is Cello Health, whose website [3] says that they provide services such as “brand and portfolio commercial strategy for biotech and pharma”, and that their clients are "24 of the top 25 pharmaceutical companies”.Authors cherry-pick to include only 4 studies reporting non-zero mortality and they claim a mortality RR of 1.11 [0.16-7.65]. However, they reported incorrect values for Niaee et al., claiming an RR of 6.51 [2.18-19.45]. The correct RR for Niaee et al. is 0.18 [0.06-0.55] (as below). After correction, their cherry-picked studies show >60% mortality reduction.Similarly, for viral clearance and NCT04392713, they report 20/41 treatment, 18/45 control, whereas the correct day 7 clearance numbers are 37/41 and 20/45 (sum of clearance @72hrs and @7 days), or 17/41 and 2/45 @72 hrs.The duration of hospital stay for Niaee et al. is also incorrectly reported, showing a lower duration for the control group.All of the errors are in one direction - incorrectly reporting lower than actual efficacy for ivermectin. Authors claim to include all RCTs excluding prophylaxis, however they only include 10 of the 24 non-prophylaxis RCTs (28 including prophylaxis). Authors actually reference meta analyses that do include the missing RCTs, so they should be aware of the missing RCTs.The PubMed search strategy provided is syntactically incorrect.For additional errors, see [4]. Also see [5].Only one of these errors has been partially fixed as of 5/29 - the Niaee RR was corrected, but the associated conclusion was not. Other errors have not been corrected. Comments on this article appear to be censored, with zero comments posted as of July 5.
Results from ivermectin use from the Misiones Ministry of Public Health
Details
News report on ivermectin use in Misiones, Argentina, showing significantly lower hospitalization and mortality, and a dose-dependent effect with improved results for those taking 0.6mg/kg.
Results from ivermectin use from the Misiones Ministry of Public Health
News report on ivermectin use in Misiones, Argentina, showing significantly lower hospitalization and mortality, and a dose-dependent effect with improved results for those taking 0.6mg/kg.
Misiones Ministry of Public Health et al., 6/22/2021, preprint, 1 author.
