Ivermectin trial shows positive results, but experts still wary

Although a top Israeli professor revealed that Ivermectin had been successfully tested on COVID-19 patients in a SA Jewish Report webinar on Thursday, 11 February, South African experts warn it’s still too early to trust this drug.

Ivermectin has been hailed by many since last year as a potential wonder drug in the fight against COVID-19. Merck, the drug’s original manufacturer, has said that too little data exists to support the use of the drug on COVID-19 patients.

In the face of mounting pressure, the SA Health Products Regulatory Authority (SAHPRA) announced last month that it had authorised a limited “compassionate and controlled-access programme” for Ivermectin to be used to treat COVID-19. Still, it stressed that only medical practitioners who applied to use the drug would be considered on a case-by-case basis, and wider access could be discussed only after large-scale testing and peer-review data became available.

The Israeli trial – like the others in South America, Bangladesh, and Egypt – was conducted in a small-scale programme.

Professor Eli Schwartz, the director of the Center for Geographic Medicine at Sheba Medical Center in Tel-Hashomer, is excited with the findings. “Ivermectin is an excellent drug that has changed many aspects of dealing with infections caused by parasites,” he says. “In many Western countries, they aren’t especially familiar with it, it’s not registered, and thus doctors are hesitant to use it.”

Schwartz shared the results of the test carried out last year for the first time on the webinar. They haven’t yet been reviewed.

“Our study looked at Ivermectin versus a placebo, using mild, non-hospitalised patients who had the virus,” he says. “Our objective was to reduce the viral shedding time and evaluate the drug’s efficacy in preventing progression.”

In a double-blind test, drug doses were determined according to the weight of each patient, and were given regularly over three days. A total of 90 patients were involved (45 in each arm of the study).

“With Ivermectin, the viral load was lowered much faster,” Schwartz says. “On day four, 57% of those who had received it were negative as opposed to 31% in the placebo group.

“From day six, more people on Ivermectin were negative, much more than in the placebo. It continued into day eight and 10. Ivermectin really had an impact, and patients quickly became negative or non-infectious.”

He also noted that some of the patients were over 60 or had risk factors, yet none of those who had taken the drug deteriorated or required hospitalisation.

Schwartz believes that the results are promising, and suggests that patients can overcome the disease faster with Ivermectin, reducing the amount of isolation required while populations wait for vaccines.

“It could prevent clinical deterioration and the need for hospitalisation,” he says. “If it proves antiviral, it can be used as a prophylactic. We should do more studies on these aspects.” He stresses, however, that the drug is no substitute for a vaccine.

Local experts and doctors are more reticent.

“The trials in other countries have been imperfect, with small numbers, varied doses, and other drugs used in addition,” says Professor Barry Schoub, the chairperson of the Ministerial Advisory Committee on COVID-19 vaccines. “We don’t really know if there’s efficacy or not, and there’s no peer-reviewed scientific evidence yet.

“It’s unlicenced, and not totally innocuous. If taken in high doses, it has the potential to be highly toxic. Unless a study is peer reviewed, it’s valueless. Until Ivermectin is tested in a proper randomised control trial, we shouldn’t use it.”

Professor Mervyn Mer, the principal specialist at Charlotte Maxeke Johannesburg Academic Hospital, says a balanced approach is needed.

“We have to question why a cheap drug hasn’t been subjected to larger trials,” he said in a recent webinar. “Many of our own colleagues are trying to take the veterinary medication, something we cannot support. A senior colleague of mine said he had taken a suggested dose and felt as strong as a horse. Several weeks later, he was severely ill with COVID-19 in intensive-care on ventilation.

“The rationale is there, but we don’t have the necessary scientific data – it’s all anecdotal. We need a balanced, sensible approach. If it works, fabulous. If not, we need to maximise what we have and continue to the best of our ability until such time as we can widely immunise patients.”

Some doctors agree with him.

“I’m not taking or prescribing Ivermectin at the moment,” says Dr Sheri Fanaroff. “It may well be effective, but the formulations currently available in South Africa aren’t regulated and thus not reliable or safe.

“If I prescribed Ivermectin and my patient developed a neurological side effect, I wouldn’t have any legal defence.”

“The Israeli study didn’t use people who are hospitalised or patients with severe disease,” says pulmonologist Anton Meyberg. “In our hospital, we had eight patients that started with mild disease, all took Ivermectin in high doses, and they all demised. They all had pulmonary and neurological manifestations, and were extremely ill.

“We have to be very careful with these small studies,” Meyberg says. “When a study is done on 90 people, that’s a phase-one trial. You need a few thousand people to see the effects of the drug. Even in Israel, Ivermectin isn’t part of the arsenal of medication and isn’t being used to treat COVID-19.”

However, GP Dr Paul Freinkel argues that there’s little downside to using the drug, and probable benefit.

“If it doesn’t work, we’ve lost little other than hope,” he says. “If it does, we’ve saved a life and, in some cases, a lifetime of disability.”

Freinkel recognises that the data generated so far by smaller trials is incomplete but maintains that very few trials show that Ivermectin doesn’t work, and they are generally underdosed.

“Even though there are no large-scale trials, what’s the chance of all the trials [of adequate dosing] all showing a benefit to using Ivermectin?” he asks.

“Andrew Hill, a senior researcher at Liverpool University, reports that the chance of an error in his meta-analysis [of the trial studies] is one in 5 000. In other words, the chance of his assertion that Ivermectin appears to work when in fact it doesn’t is only one in 5 000. That’s a one in 5 000 chance that it doesn’t decrease the chance of people dying,” Freinkel says.

“As my patients get sicker, I wonder about the downside to using it versus the 4 999 in 5 000 chance that it has a benefit. Must I watch a patient die knowing there is so little downside of her taking a drug that may cure her? The law says so.”

Because recommending Ivermectin carries the risk of prosecution, Freinkel suggests that Ivermectin should be approved for human use on parasites, where the efficacy and safety data are incontrovertible.

“This would allow doctors to legally and ethically use the medication off-label, as they do in most other countries,” he says.