Working on similar lines as hydroxychloroquine, ivermectin had been promoted as a possible COVID-19 antiviral. With insufficient evidence supporting the drug's efficacy and ongoing research, the antiparasitic drug currently lacks the possibility of being completely approved as an effective solution to curb COVID-19.

Is Ivermectin going the way of Hydroxychloroquine?

With the advent of secure and efficient COVID-19 vaccinations, which seem to pave the way for a post-pandemic future, one is unsure if it is still worthwhile to investigate unproven COVID-19 therapies. After all, it has been well over a year and we now have a much better understanding of what works best to avoid and cure SARS-CoV-2 infections. However, it's remarkable that there are still ardent proponents of therapies that lack clear evidence of benefit. Ivermectin is included in this group.

Ivermectin has been hailed as a miracle cure for almost as long as the global pandemic has existed, and the enthusiasm persists (in some), despite mounting evidence on the contrary. Notably, substantial improvement has been made in treating COVID-19 over the last year, including the refashioning of other medications that have been shown to function (e.g., dexamethasone, tocilizumab). During the same time period, medications such as hydroxychloroquine have been shown to be inactive. It is possible that the hydroxychloroquine group has shifted their focus.

Ivermectin's use is supported by scant evidence

Ivermectin is a medication used to treat parasitic infections. It is used in the treatment of intestinal strongyloidiasis (threadworm infection caused by Strongyloides stercoralis) and even onchocerciasis (river blindness, caused by the parasitic worm Onchocerca volvulus, and spread by the Simulium blackfly). Ivermectin has piqued interest since the initial periods of the COVID-19 pandemic when it was discovered that it had antiviral effects against the SARS-CoV-2 virus at elevated concentrations.

The discovery, however, contained a critical warning flag. A few weeks after the original finding was reported, a brief article in the British Journal of Clinical Pharmacology discussed the factors to remember when using ivermectin as an antiviral. Although it recognised the antiviral effects of high doses of the drug in laboratory (in vitro) studies, it indicated that such levels of the drug would certainly not be present in blood plasma due to the drug's close association with blood proteins. Even administering 8.5 times the FDA-approved dose (1700 mcg/kg) resulting in blood level well below the antiviral dose recognised. A medicine would have little benefit if it does not achieve adequate levels in the blood or plasma.

The first experiments were small and underpowered, making it impossible to find anything. This chart study (not a randomized, clinical trial) of hospitalized patients receiving with or without ivermectin, written in October 2020, is one of the most highly cited articles. Ivermectin was linked to lower mortality, particularly in patients with extreme pulmonary involvement, according to the researchers. Patients who obtained ivermectin were often more likely to take steroid medications (which have been shown to decrease COVID-19 mortality), suggesting that the utilisation of steroids might have influenced the results. The authors were right in recommending that these results be validated in a randomised controlled trial.

One additional, randomised, prospective experiment was this one, which was released in December 2020. This small study randomised 72 hospitalised patients in Bangladesh to receive either ivermectin (12 mg daily for 5 days), ivermectin (12 mg daily for five days) in combination with doxycycline (an antibiotic), or a placebo. The investigators observed that the five-day ivermectin arm cleared viruses more quickly than the placebo arm. The experiment did not examine any other endpoints than protection (it was well accepted), and the investigators indicated that larger trials would be necessary.

In March 2021, another randomised clinical trial examined the application of ivermectin in people with mild COVID-19 infection (i.e., those who were not hospitalised). This was a much bigger study involving 476 patients who received either ivermectin 300 g/kg daily for five days or a placebo. (Before continuing, refer to the picture above and look up 300 g/kg.) The researchers discovered that ivermectin had little effect on the time required for symptoms to resolve.

A health technology review released on February 8, 2021, tried to summarize and examine all available literature proof for ivermectin up to January 5, 2021, in a thorough and systematic manner. It discovered a total of six publications and concluded as follows: The primary trials reported in this study, including those included in the [systematic review], were considered to have a significant risk of bias, resulting in a very poor level of evidence that precludes drawing any firm conclusions on whether ivermectin can minimise all-cause death, reduce clinical symptoms and hospital admission, and improve viral clearing in patients with COVID-19.

The included recommendations currently prohibit the use of ivermectin to treat COVID-19 due to the absence of solid evidence. It is conceivable that the reported variability in ivermectin effectiveness in recent clinical trials was due in part to inadequate drug concentrations in patients' plasma when the accepted dosage for parasitic infections was used to address COVID-19. To draw accurate conclusions about the benefits and risks of ivermectin for the protection and management of COVID-19, well-conducted dose-response studies are required. Before then, the report's current evidence should be interpreted cautiously.

Even the pharmaceutical industry advises against it

Ivermectin has been well accepted, with no overdose deaths recorded to date. Significant exposure to veterinary forms of ivermectin at far higher levels has resulted in a variety of adverse effects ranging from rash and headache to more serious effects such as seizures. The FDA also issued a warning against the use of ivermectin, stating that several individuals have been hospitalised as a result of its use.

In February 2021, the NIH reported on the lack of evidence of its COVID-19 Clinical Guidelines:

"There is inadequate evidence to make a recommendation for or against the use of ivermectin in the treatment of COVID-19 by the COVID-19 Treatment Guidelines Panel (the Panel). To provide more specific, evidence-based guidelines on the role of ivermectin in the treatment of COVID-19, results from appropriately powered well-designed, and well-conducted clinical studies are warranted."

Given the drug's acceptable adverse effect profile at recommended doses and widespread interest, one would expect the manufacturer to be positive, if not dismissive, about the drug's potential for usage. Merck, the manufacturer of ivermectin, issued the following announcement regarding the medication in February.

Project scientists continue to closely review the results of all current and new trials on ivermectin's effectiveness and protection in the treatment of COVID-19. It is important to note that our review has so far established the following:

There is no scientific evidence from preclinical trials to support a possible therapeutic activity against COVID-19. There is no evidence to support therapeutic activity or effectiveness in patients with COVID-19 disorder, and there is an alarming shortage of evidence on protection in the majority of reports.

We conclude that the available evidence does not confirm the protection and effectiveness of ivermectin outside the doses and populations specified in the prescription information accepted by the regulatory agency.

Bottomline- Ivermectin has not been shown to be effective against COVID-19

The outbreak of the COVID-19 pandemic sparked widespread concern in repurposing generic medications to minimise contamination risk or seriousness. Although some medications have been successfully reconfigured and are still used routinely to treat COVID-19, several others have been tried and shown to be unsuccessful. Anecdotal facts and theories are excellent places to begin doing studies. However, when proof accumulates, we must prioritise the most robust analyses to guide our decision-making. As with hydroxychloroquine, there is insufficient data to suggest that ivermectin has any clinically meaningful role in the treatment of COVID-19.