Insufficient evidence to support ivermectin as COVID-19 treatment

Ivermectin is a broad-spectrum anti-parasitic drug that can be used to treat scabies, parasitic worms and head lice.
 
It has also been shown to be effective in-vitro against a broad range of viruses, including HIV, dengue, influenza and Zika virus.
 
Interest in ivermectin as a potential treatment for coronavirus was sparked following research that found a single treatment led to a significant reduction of the virus in-vitro.
 
Led by Monash University researchers in collaboration with the Doherty Institute and published on 3 April in Antiviral Research, the research found 5 µM of ivermectin dramatically reduced in-vitro viral replication of SARS-CoV-2 by approximately 5000-fold over 48 hours.
 
Dr Kylie Wagstaff is a senior research fellow at Monash Biomedicine Discovery Institute and one of the researchers involved in the study.
 
‘We found that even a single dose could essentially remove all viral RNA by 48 hours, and that even at 24 hours there was a really significant reduction in it,’ she said.
 
The authors say ivermectin binds to, and destablises, the receptor responsible for transmitting viral proteins into the host cell nucleus.
 
‘This likely results in reduced inhibition of the antiviral responses, leading to a normal, more efficient antiviral response,’ the study authors wrote.
 
Dr Wagstaff says these results are encouraging.
 
‘Ivermectin is very widely used and seen as a safe drug,’ she said.
 
‘We need to figure out now whether the dosage you can use it at in humans will be effective – that’s the next step.
 
‘In times when we’re having a global pandemic and there isn’t an approved treatment, if we had a compound that was already available around the world then that might help people sooner. Realistically it’s going to be a while before a vaccine is broadly available.’
 
While publication of this research led to widespread interest of ivermectin as a potential therapy for COVID-19, it also sparked concern about potential misuse of the drug.
 
The US Food and Drug Administration (FDA) shared that concern, issuing a warning on 10 April that ivermectin in veterinary products should not be used for human therapy.
 
The letter states the research did not involve giving ivermectin to people or animals, and that it only stopped replication of SARS-CoV-2 ‘in a petri dish’.
 
Two letters to the editor of Antiviral Research were also published in response to the initial research.
 
Among other issues, those letters raised concerns about the potential dose of ivermectin needed to be effective in-vivo rather than in-vitro.
 
Questions were also raised regarding the relevance of in-vitro results in a clinical context.
 
‘In vitro promise leads to clinical failure in the vast majority of cases, and in the volatile environment of the current pandemic, it is critical that we are sensitive to the implications of our communication and apply our resources to compounds most likely to succeed,’ the authors of one of the letters wrote.
 
Reports in July indicate officials in Brazil included the anti-parasitic drug in so-called ‘COVID kits’ – along with hydroxychloroquine, the antibiotic azithromycin, zinc, and vitamin C – that were distributed in cities in the south, central-west, and north-east parts of the country.
 
Sydney gastroenterologist Professor Thomas Borody has since reignited interest in the topic with a 7 August interview on Sky News Australia in which he said ivermectin, when combined with doxycycline and zinc, may be an effective treatment for the virus.
 
‘There are a number of studies that are amazingly successful – we’re talking close to 100%,’ Professor Borody told Sky News.
 
He said this treatment has not been used in Australian patients, but that it has been used successfully in China and Bangladesh.
 
‘So I am behind the ivermectin, doxycycline, zinc treatment because it has very few side effects, and is a real killer of coronavirus,’ Professor Borody said.

Associate Professor Steven Tong says initial laboratory studies suggest ivermectin may play a role in combatting COVID-19 but more research is needed.
 
Associate Professor Steven Tong is an infectious diseases clinician at Royal Melbourne Hospital, the principal investigator for the AustralaSian COVID-19 Trial (ASCOT) and a co-lead of clinical research at the Doherty Institute.
 
He has not seen any clinical evidence to support Professor Borody’s claims.
 
‘At this stage I’m not aware of that data,’ he told newsGP. ‘And if there is such convincing data, I think it would be helpful for that to be shared with everyone.’
 
Associate Professor Tong says he is aware of a study performed in Bangladesh involving ivermectin.
 
‘But it was pretty poor quality, as far as I understand,’ he said.
 
While there are discussions on the potential use of ivermectin as a therapy for COVID-19 in humans, Associate Professor Tong has concerns about its use in that context.
 
‘The initial studies seem to suggest you need a very high level of ivermectin to be able to reduce replication of the virus, and those levels in those initial studies are very difficult or impossible to achieve in a person,’ he said.
 
He is also concerned that these laboratory findings were not performed on human cells.
 
‘They were done initially with monkey cells, so we await work with human cell lines to confirm the effect and confirm whether the dose is achievable,’ he said.
 
Following on from the initial paper, researchers from Monash University and the Peter Doherty Institute of Infection and Immunity are continuing to investigate the use of ivermectin as a potential treatment for COVID-19 with current ongoing research.
 
Their aim is to move from in-vitro phase to pre-clinical trials soon.
 
‘We are conducting a range of optimisation experiments that, if positive, will determine the best dosage and treatment regimen to move forward into clinical trials,’ Dr Wagstaff said.
 
Associate Professor Tong is aware of other trials looking into ivermectin as a potential COVID-19 treatment in South America and elsewhere.
 
He says there even are reports that some countries are using the drug ‘more broadly’ as a treatment for COVID-19.
 
However, Associate Professor Tong says there is currently insufficient evidence to show ivermectin can be used as therapy for COVID-19 and that randomised controlled trials are needed to investigate this area.
 
‘And until we get that level of evidence, these agents should only be used in the context of a clinical trial,’ he said.
 
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