I started writing about the drug ivermectin against COVID-19 more than two years ago. That’s because Australian researchers reported that this drug for parasites had strong antiviral activity vs. the coronavirus. That was test tube research (Antiviral Research, April 3, 2020). I hoped that clinical trials might demonstrate that this old drug could either prevent COVID, shorten its duration or lessen the severity of the infection. More important, I wished that ivermectin could keep people out of the hospital and save lives. More than two years have passed, and like nearly everything else associated with the pandemic, views on ivermectin became polarized. Many people continue to believe the drug is a cure for COVID-19. The data suggest otherwise. The latest and largest randomized clinical trial was posted online on June 12, 2022 (MedRxiv). What does it tell us about ivermectin?
COVID-19 vs. Ivermectin?
I have lost count of the number of messages we have received insisting that ivermectin is an absolute cure for COVID. Here are just a couple:
Linda has no doubt that ivermectin cured her:
“If COVID cases start to rise again, I will not change anything. I will not get boosted. Nor will I wear a mask or stay home. I contracted COVID late Feb 2022, took ivermectin early in the course of the virus and in 12 hours had no symptoms. I’ll take ivermectin again if I catch COVID again.”
“Early treatment [with ivermectin] would have saved hundreds of thousands of lives.”
D0n offers his friends as proof of ivermectin’s effectiveness:
“I have several friends who were doing poorly with COVID, until they took Ivermectin. All have fully recovered.”
Why Wait for RCTs of Ivermectin?
The course of illness with COVID-19 is highly variable. Some people remain asymptomatic even though they test positive. Others have mild symptoms, barely worse than a “common” cold. Many people become very sick with a fever, chills, cough, fatigue and serious breathing problems. Some end up in the hospital while others die. At last count, hundreds are still dying daily from complications of COVID.
The anecdotes that people share on our website are not scientific. They may be interesting, but they do not tell the whole story. Both Linda and Don may believe that ivermectin is effective against COVID, but that is not enough to endorse the treatment.
The only way to truly assess the effectiveness of ivermectin (or any drug, for that matter) is to perform large, randomized controlled trials (RCTs). Neither the patients nor the investigators know who gets what. Such RCTs are not perfect, but they are the best tool we have because they do away with politics and preconceptions that might influence the outcome.
What Do the New Data Reveal About Ivermectin?
Many readers state that they do not trust drug company-sponsored clinical trials. We get that. We have been critical ourselves. But the latest ivermectin RCT (MedRxiv, June 12, 2022) was conducted by researchers at Vanderbilt and Duke University. They had no horse in the race.
Patients were recruited from 93 sites in the US. 817 were randomized to receive ivermectin while 774 were given placebo pills. This is the largest randomized clinical trial to date!
Here is the bottom line:
“Conclusions: Ivermectin dosed at 400 μg/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.”
Dr. Adrian Hernandez is executive director of the Duke Clinical Research Institute.
He was the principal investigator of the ivermectin clinical trial and added this:
“There was no significant benefit in our primary endpoint of resolution of symptoms in mild-to-moderate COVID-19 illness. Overall, most people improved their symptoms whether they took ivermectin or not. Given these results, there does not appear to be a role for ivermectin outside of a clinical trial setting, especially considering other available options with proven reduction in hospitalizations and death.”
Drilling Down on the Data:
If ivermectin were the cure for COVID, we should have seen very clear evidence that patients got better way faster than people on placebo. That did not happen.
People taking the sugar pills got better in about 11.5 days. Those on ivermectin recovered in about 11 days. What was the difference between placebo and ivermectin? About half a day (12 hours). Not a dramatic “cure.”
For the metrics that really mattered, hospitalization or death, there was no statistically significant difference between the patients on placebo and those who got ivermectin. There was just one death during the clinical trial, and it happened to a patient on ivermectin.
Was There a Glimmer of Good News for Ivermectin?
There was one situation in which ivermectin might have been helpful, however. Some of the volunteers with severe COVID symptoms seemed to recover a little bit faster, but this result requires further research for confirmation because the numbers were so small. The investigators plan to increase the dose and duration of ivermectin among severely ill patients to test that hypothesis.
Believe me when I tell you that I would love for ivermectin to work against COVID, even if the benefit is modest. That’s because I love this drug. You may find its history as fascinating as I do.
Where Did This Amazing Drug for Parasites Come from?
Please indulge me for a quick minute. In case you have not read anything about this fascinating medicine, here is a quick historical overview:
Fifty years ago a Japanese microbiologist tested some dirt from a golf course near Honshu. He and his colleague William Campbell at Merck discovered that unique bacteria in that soil had anti-parasitic activity against roundworms in mice. Their research led to a Nobel Prize in Physiology or Medicine in 2015.
Merck introduced ivermectin for treating parasites in animals in 1981. Many dog lovers still administer a monthly dose of ivermectin (Heartgard) to their canine companions to prevent heartworm.
Then the company discovered that ivermectin could also fight off the parasite Onchocerca volvulus that causes “river blindness” in humans. Infected Simulium black flies carry the larvae of this worm. It causes untold misery in Africa and Latin America.
Symptoms include skin rashes, nodules and horrific itching. Inflammation in the eye can lead to clouding of the cornea, optic nerve damage and ultimately blindness. Public health agencies approved ivermectin to treat people with river blindness in 1987. The brand name was Mectizan. It has saved the sight of millions of people in Africa and Latin America. Some experts consider it a wonder drug on a par with aspirin and penicillin.
Lice and Scabies: Ivermectin? Really!
In addition, ivermectin can help treat conditions beyond river blindness and heartworm disease. Although most of these are in the form of filaria, tiny thread-like worms, it is also effective against lice and scabies.
A review in the Journal of Drugs in Dermatology (March, 2016) states:
“Numerous studies report low rates of adverse events, as an oral treatment for parasitic infections, scabies and head lice. Ivermectin has been used off-label to treat diseases associated with Demodex mites, such as blepharitis and demodicidosis. New evidence has linked Demodex mites to rosacea, a chronic inflammatory disease. Ivermectin has recently received FDA and EU approval for the treatment of adult patients with inflammatory lesions of rosacea, a disease in which this agent has been shown to be well tolerated.”
None of this got anyone particularly excited. But then COVID-19 hit.
The Coronavirus and Ivermectin?
There have been dozens of publications about ivermectin vs. COVID-19. There are enthusiasts and critics. Like just about everything related to this virus, there are strong emotions. We don’t understand why this amazing drug has been caught in the crossfire, but it has.
A Drug for Parasites Has Antiviral Activity:
It may seem surprising that a drug for parasites would knock out viruses. However, scientists have previously found that it can slow proliferation of the virus that causes dengue fever.
Australian researchers have found that ivermectin has strong antiviral activity in the lab (Antiviral Research, online, April 3, 2020):
“Taken together these results demonstrate that ivermectin has antiviral action against the SARS-CoV-2 clinical isolate in vitro, with a single dose able to control viral replication within 24–48 h in our system…Ultimately, development of an effective anti-viral for SARS-CoV-2, if given to patients early in infection, could help to limit the viral load, prevent severe disease progression and limit person-person transmission…This Brief Report raises the possibility that ivermectin could be a useful antiviral to limit SARS-CoV-2, in similar fashion to those already reported…”
A Randomized Controlled Trial of a Drug for Parasites:
Two years ago we wrote:
“Unfortunately, this basic laboratory research is still far from uncovering clinical efficacy. Since ivermectin has been used in human medicine for decades, clinicians already know quite a bit about its side effects. However, as with most of the other drugs currently under study, we won’t know if it works against COVID-19 until clinical trials are conducted.”
A year later we had a sliver of clinical research to support ivermectin against COVID-19 (EClinicalMedicine, Jan. 19, 2021). Researchers treated 24 COVID patients in Pamplona, Spain. They randomly assigned half of the participants to take ivermectin. The others took placebo pills.
Patients who received ivermectin had substantially less viral load after four days. Seven days after treatment with the drug, the viral load was 18 times lower than in the placebo patients. The treated patients were half as likely to lose their sense of taste and smell and a third less likely to develop a cough.
Big Clinical Trial Results! What Happened to Ivermectin?
Let’s be honest. A clinical trial involving 24 COVID patients in Pamplona, Spain, is not enough to draw any meaningful conclusions. Other clinical trials followed but they produced mixed results and there were serious questions about methodology and interpretation.
One set of authors initially published a meta-analysis of research that supported the use of ivermectin against COVID (Open Forum Infectious Diseases, July 6, 2021).
They later retracted the article because:
“These instances suggest that the data available to support the use of ivermectin for COVID-19 is not reliable. In July 2021, after the potentially fraudulent studies were identified, we retracted our published meta-analysis and began working on an updated analysis, assessing the effects of stratifying by trial quality on the overall results.”
Once the authors eliminated the fraudulent or questionable research, they found that:
“…ivermectin results in a non-significant 4% increase in survival.”
“These observations demonstrate that the significant effect of ivermectin on survival was dependent on the inclusion of studies with a high risk of bias or potential medical fraud.”
What About Other Results with Ivermectin?
One of the biggest randomized clinical trials was published in the New England Journal of Medicine (March 30, 2022).
The researchers recruited “symptomatic SARS-CoV-2–positive adults recruited from 12 public health clinics in Brazil.”
“A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157).”
And the envelope please! The authors conclude:
“We did not find a significantly or clinically meaningful lower risk of medical admission to a hospital or prolonged emergency department observation (primary composite outcome) with ivermectin administered for 3 days at a dose of 400 μg per kilogram per day than with placebo. We found no important effects of treatment with ivermectin on the secondary outcomes.”
Other Studies of Ivermectin?
Another “controlled, clinical, randomized, double-blind trial that included hospitalized patients with COVID-19-induced pneumonia, without severe respiratory failure” was published recently in the journal Infectious Disease Reports (March 3, 2022).
“In non-critical hospitalized patients with COVID-19 pneumonia, neither ivermectin nor hydroxychloroquine decreases the number of in-hospital days, respiratory deterioration, or deaths.”
But Wait…There’s More:
Investigators writing in JAMA Internal Medicine (Feb. 18, 2022) describe the reasoning behind their study:
“Importance: Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19. Evidence-based data to recommend either for or against the use of ivermectin are needed.
“Objective: To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19.
“Conclusions and relevance: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19.”
Let me be perfectly clear. I think ivermectin is a fabulous drug! You can read why at this link. It works well against river blindness in people and heartworm disease in dogs. It also has utility against hard-to-treat lice and scabies and may be helpful topically against rosacea. Now a large, well-controlled trial demonstrates that ivermectin does not help people avoid hospitalization. If it speeds healing, the benefit is modest (12 hours).
We received this message from Dr. E, a researcher at Merck, the company that originally developed ivermectin:
“I worked for Merck in the 1980’s and you’re right, ivermectin is a fantastic drug for certain conditions. Just not COVID. As always, you have written a well researched, well referenced & well written article on this topic. Thank you for being the ‘town crier’ of science and putting it all in perspective for all.”
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