Ivermectin for COVID-19: Worth a Try?

Ivermectin, an antiparasitic used to treat river blindness, is prescribed off-label to treat COVID-19 in some parts of the world, but regulatory agencies recommend that randomized controlled trials be conducted before widespread use.

On April 3, researchers from Monash University in Australia demonstrated that ivermectin could inhibit SARS-CoV-2 in cell culture, sparking a wave of enthusiasm for reusing the drug as an antiviral at a time when several alternatives were available. Although the concentrations of ivermectin used in vitro are much greater than physiological levels in human clinical use, the positive findings quickly circulated and have since been cited in more than 450 publications.

Some doctors, citing the study, have begun to integrate the off-label use of ivermectin into their COVID-19 treatment protocols, and in Peru and Bolivia, the health ministry has officially authorized the drug for this indication. Although the drug is relatively safe, some scientists are concerned that doctors are putting a cart before horses in prescribing ivermectin for COVID-19.

“Pandemics create a sense of urgency and we tend to take shortcuts, and that’s fine, but you don’t take shortcuts,” says Carlos Chaccour, MD, PhD, of the Barcelona Institute for Global Health in Spain, who studies ivermectin in the context of tropical disease.

“There needs to be scientific rigor. One might say, ‘What’s the harm? It’s a safe drug,’ but no drug is free from side effects,” he said.

Although the mechanism of action of ivermectin as an antiviral is unknown, ivermectin also inhibits viral replication with other RNA viruses, including dengue virus and Zika virus.

Ivermectin may cause gastrointestinal side effects or skin rashes, and may be neurotoxic in rare circumstances. In a May 1 post from the FDA, the agency said using drugs to prevent or treat COVID-19 “should be avoided” in the absence of clinical trials.

The agency also issued a warning letter 1 week after the in vitro study was published warning against the use of ivermectin formulations for animals. Presumably, the letter was meant to protect the public from misinformation, after a man died in March from taking chloroquine phosphate, an aquarium cleaner, when hydroxychloroquine (HCQ) made headlines.

In Peru, demand for the drug surged after authorization, leading some to turn to veterinary drug formulations, which are used to treat liver flukes and can cause serious harm to humans.

“The FDA is concerned about the health of consumers who may self-medicate by taking ivermectin products intended for animals, thinking they may be substitutes for ivermectin intended for humans,” the agency said. “People should not use veterinary drugs, as the FDA only evaluates their safety and effectiveness on the specific animal species they are labeled with.”

However, in doses used off-label for scabies, for example, ivermectin has a low side-effect profile. Without many alternatives available, some doctors are moving forward from formal trials and starting to prescribe them for COVID-19.

Positive Signal in Florida

Jean-Jacques Rajter, MD, a pulmonary care physician at Broward Health Medical Center in Fort Lauderdale, Florida, began using ivermectin to treat COVID-19 in critically ill patients after seeing promising findings from an in vitro study in April.

“At the time, dexamethasone, remdesivir and convalescent plasma weren’t really on the market or were inaccessible because not enough people had recovered,” Rajter said. MedPage Today. “No other.”

Rajter said he treated 15-20 patients during the second half of April on standard doses of scabies ivermectin and had a very high success rate. Soon after, colleagues at Broward Health also began prescribing ivermectin, and Rajter and his wife and colleague, Juliana Cepelowicz Rajter, MD, co-authored a retrospective, preprinted, study of 280 patients, published in June.

In the study, which was not peer reviewed, ivermectin was associated with a survival benefit among patients with severe COVID-19 compared to usual care. Associations remained after adjusting for differences between groups, including use of azithromycin, hydroxychloroquine, and zinc, which were common.

“When this was released in preprinted, other investigators around the world took notice in Peru, Brazil, Colombia, Bangladesh, Mexico and Iraq,” said Jean-Jacques Rajter. “The success story we had in early April has been duplicated in other small studies around the world.”

Experiments conducted in Iraq, Bangladesh, and Mexico have shown positive results with ivermectin. But studies in Bangladesh and Mexico did not have a control group, and the study in Iraq only treated 16 patients with ivermectin.

Matthew Spinelli, MD, of the University of California, San Francisco, says: MedPage Today in an email that positive anecdotal reports are “difficult to interpret given that most infected patients will self-limit, and clinical manifestations vary widely for COVID-19.”

Next HCQ?

Parallels have been drawn with ivermectin and HCQ: Both reduce viral load in vitro and generate signals that cause them to be prescribed under compassionate use, says Zeno Bisoffi, MD, PhD, of the University of Verona in Italy.

“There are several results from observational studies that claim that [hydroxychloroquine] worked, but actually it was a small study with very heavy methodological flaws,” Bisoffi . said MedPage Today. “Nevertheless, they are quoted everywhere, so most doctors around the world use hydroxychloroquine without evidence.”

“This is a mistake we want to avoid with ivermectin,” Bisoffi says.

The two drugs were also entangled in the Surgisphere Corp scandal. notoriously cruel. At the end of May, the flawed data of the shadow company was used in the recall since then Lancet studies that found HCQ to be associated with an increased risk of death and ventricular arrhythmias.

A little-known precast study of 169 hospitals worldwide also used Surgisphere data to show that ivermectin reduces the need for mechanical ventilation and mortality. Like the HCQ study, the scientific community identified discrepancies in Surgisphere’s ivermectin data, and the paper was withdrawn — but not before it was downloaded more than 15,000 times.

The paper influenced policy decisions in Latin America and was cited in a white paper advocating ivermectin for inclusion in Peruvian medicine guidelines.

Positive findings from another study in India are also being evaluated by the country’s medical review board, Print reported. In Australia, a renowned gastroenterologist who reuses drugs, Thomas Borody, MD, PhD, director of the Center for Digestive Diseases in Sydney, Australia, supports ivermectin as one part of a triple drug therapy, along with doxycycline and zinc, for outpatients. Street. Coronavirus case.

“Ivermectin has been used in billions of prescriptions to date, and even at high doses there are very few side effects when used for things like scabies,” says Borody. MedPage Today. “This thing in combination with all three working really well, I believe this is the path we have to go.”

Call for Further Research

While ICU doctors may see ivermectin as something worth trying, others believe the evidence is too scant.

The drug should not be phased out, but neither is it ready for widespread clinical use, Chaccour said. For example, it’s still unclear whether it’s safe to use in the context of high-inflammatory syndromes, such as COVID-19, or in combination with other medications, he said.

Rajter said he initially used ivermectin as a “measure of hopelessness.” But now that he’s seen positive results in his hospital network, he’s frustrated by the deliberately slow review process.

Certain medications are being expedited by the FDA, while “other treatments that have been shown to be moderately effective — such as ivermectin — have yet to be seen,” Rajter said.

Currently, there are more than 30 clinical trials testing ivermectin for COVID-19. Bisoffi is investigating high doses of ivermectin for mild infections and Chaccour is also conducting trials in Spain. A team at Johns Hopkins University compared ivermectin versus bicalutamide and usual care among hospitalized COVID-19 patients.

Whether ivermectin passes the test in a randomized controlled setting remains to be seen, but scientists seem to agree that ivermectin guarantees at least that.

“It is unfortunate that so few randomized controlled trials have been conducted in the US on a potential treatment like this,” Spinelli said.

Last Updated 04 November 2020

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    Elizabeth Hlavinka covers clinical news, features and investigative work for MedPage Today. He also produces episodes for the Anamnesis podcast. Follow

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