Ivermectin has not been shown to be effective in any large and well designed clinical trial. Several studies that initially showed effectiveness have been retracted.
"The global demand for prophylactic and treatment options for COVID-19 has in turn created a demand for both randomized clinical trials, and the synthesis of those trials into meta-analyses by systematic review. This process has been fraught, and has demonstrated the inherent risks in current approaches and accepted standards of quantitative evidence synthesis when dealing with high volumes of recent, often unpublished trial data of variable quality,", says a group of 5 scientists in "The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable" (https://www.nature.com/articles/s41591-021-01535-y)
The analysis describes several studies that were incorporated into major meta-analyses before they were ultimately retracted. "We described several irregularities in the data that could not be consistent with them being experimentally derived" and "We also raised concerns about unexpected stratification across baseline variables in another randomized controlled trial for ivermectin6, which were highly suggestive of randomization failure"
[preprint] "Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 mcg/kg daily for 6 days, compared with placebo did not improve time to recovery." (double-blind placebo controlled trial, 1206 participants with confirmed COVID-19 for ≥7 days and multiple symptoms were enrolled)"
"Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19."
"Ivermectin dosed at 400 mcg/kg daily for 3 days resulted in less than one day of shortening of symptoms and did not lower incidence of hospitalization or death among outpatients with COVID-19 in the United States during the delta and omicron variant time periods."
"Randomization to the ivermectin arm was stopped after enrolling 205 patients into all arms, as the prespecified futility threshold was reached. Compared with the no study drug arm, the mean estimated SARS-CoV-2 viral clearance following ivermectin was 9.1% slower."
"Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19."
"A systematic review and meta-analysis of studies was performed based on the PRISMA 2020 statement criteria... Ivermectin did not have any significant effect on outcomes of COVID-19 patients and as WHO recommends, use of ivermectin should be limited to clinical trials."
"A high dose of ivermectin (400–600 µg/kg/d) for 3 days did not show a significant benefit for the prevention of SARS-CoV-2 infection. Similarly, early treatment with the same dose and duration of ivermectin did not reduce disease progression or hospitalization in patients with mild-to-moderate COVID-19 compared with the placebo group."
"Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19."
"In this study of non-critically ill patients with pneumonia secondary to COVID-19 and fulfilling hospitalization criteria, treatment with hydroxychloroquine or ivermectin was not superior to placebo, neither in terms of hospitalization duration nor in progression to severe respiratory failure or death."
"a 5-day course of oral ivermectin administered during the first week of illness did not reduce the risk of developing severe disease compared with standard of care alone."
"High-dose ivermectin was safe but did not show efficacy to reduce viral load."
"Among adults with mild coronavirus disease 2019, a 5 d course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild coronavirus disease 2019."
"A large Egyptian study of ivermectin for COVID-19 patients has been retracted over concerns of plagiarism and serious problems with their raw data... 'we were presented with evidence of both plagiarism and anomalies in the dataset associated with the study, neither of which could reasonably be addressed by the author issuing a revised version of the paper.'"
"The authors of a study purportedly showing that ivermectin could treat patients with SARS-CoV-2 have retracted their paper after acknowledging that their data were garbled. The paper, “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,” appeared in the journal Viruses..."
"Several other studies that claim a clinical benefit for ivermectin are similarly fraught, and contain impossible numbers in their results, unexplainable mismatches between trial registry updates and published patient demographics, purported timelines that are not consistent with the veracity of the data collection, and substantial methodological weaknesses. We expect further studies supporting ivermectin to be withdrawn over the coming months."
In vitro studies show that Ivermectin has anti-viral effects against SARS-CoV-2, but the human body does not work the same way as glass containers. Once you have positive results in vitro, you must proceed to human studies before any practical conclusion can be drawn.
Example of a study showing positive results for Ivermectin in vitro: https://www.nature.com/articles/s41429-020-0336-z
ivmmeta.com, c19ivermectin.com, and other websites offer crude meta-analyses of Ivermectin studies. These analyses are not based on any systematic reviews of the individual studies. Only the most rudimentary classifications and exclusions have been employed.
"These websites show pooled estimates suggesting significant benefits with ivermectin, which has resulted in confusion for clinicians, patients and even decision-makers. This is usually a problem when performing meta-analyses which are not based in rigorous systematic reviews, often leading to spread spurious or fallacious findings."
Gideon Meyerowitz-Katz (@GidMK) is an epidemiologist who has written a thread about ivmmeta.com on Twitter:
One of the many observations from the above thread:
"[this] trial found NO BENEFIT FOR IVERMECTIN, but this has been reported and included into ivmmeta dot com as a hugely beneficial result... it's not publication bias, it's that the authors appear to have generally chosen whichever result makes ivermectin look better to include in their model"
"Relying on low-quality or questionable studies in the current global climate presents severe and immediate harms. The enormous impact of COVID-19 and the consequent urgent need to demonstrate the clinical efficacy of new therapeutic options provides fertile ground for even poorly evidenced claims of efficacy to be amplified, both in the scientific literature and on social media. This context can lead to the rapid translation of almost any apparently favorable conclusion from a relatively weak trial or set of trials into widespread clinical practice and public policy."
The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable (2021-09-22)
FDA: Why You Should Not Use Ivermectin to Treat or Prevent COVID-19 (2021-12-10)
Claims that results in Africa show that Ivermectin works are not supported by evidence.
Africa CDC statement on the use of Invermectin for COVID-19 confirms that there is no evidence that Ivermectin is effective for treatment of Covid-19.
There are other explanations for low mortality in Africa...
"Africa’s lower COVID-19 mortality rate is due to the lower population mean age, lower life expectancy, lower pre-COVID-19 era ‘65yr+ mortality rate’, and smaller pool of people surviving and living with cardiovascular diseases."
"...in SSA [sub-Saharan Africa] the overall death rate is lower than in most other regions primarily due to the demographic structure with a low median age and a small percentage of vulnerable elderly" (see link for additional factors)
"Around 90% of deceased people tested at a Lusaka facility during coronavirus surges were positive for SARS-CoV-2 infection, suggesting flaws in the idea of an ‘African paradox’."
Dr. Andrew Hill was an early supporter of Ivermectin and was involved in research to establish effectiveness. His story turns dark when he realized that many of the studies that showed efficacy for Ivermectin were either fraudulent or flawed.
"We then found several examples of medical fraud in the clinical trials of ivermectin: some of the databases had been simply made up by unscrupulous doctors. When we filtered out all the poor-quality clinical trials, there was no longer any clinical benefit for ivermectin."
– Dr. Andrew Hill writing for The Guardian https://amp.theguardian.com/world/2021/oct/13/how-my-ivermectin-research-led-to-twitter-death-threats
The above article includes descriptions of some of the abuse Dr. Hill has endured for telling the truth.