Insufficient evidence to support ivermectin as COVID-19 treatment

Evelyn Lewin

15/08/2020 4:23:57 PM

Recent research led to the anti-parasitic being discussed as a potential treatment, but experts say more research is currently needed.

Blister pack of ivermectin
Ivermectin sold out from pharmacies in Brazil after it was suggested it was an effective for treatment of COVID-19. (Image: AAP)

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.

Steven-Tong-article.jpgAssociate 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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Dr Arun Kumar Saha   14/08/2020 9:53:40 AM

I understand that this regiem is using in india and I was told that it is working
We have nothing to loose to give a trail in this country with pt consent

Dr Dharminder Jit Singh   14/08/2020 12:14:57 PM

Patient may be given the option of this treatment and explained that it is on a trial basis. There is minimal harm as there is no new drugs in this treatment option. I feel it should be given early rather than when patient is on a ventilator. As with a some of other viruses, this virus possibly does not respond to treatment after the initial phase of 72 hours and becomes supportive management only then.

Dr Ragupathy Renganathan   17/08/2020 1:53:13 PM

Interesting to note in the " developing countries" where there is NOT much of medico-legal implication ,they are daring to administer known medications( with not so much of sinister side-effects.)
Just like Hydroxychloroquine which at the initial stage of Covid19 epidemic was used in some Western countries and has faded away due the cry of side-effects.
In a desperate situation every country is trying "some medication" with some clinical inclination and knowledge of the drug-more so if side effects are not "disastrous".
I support these trials, after all despite all advances in medicine there were many including the incidental discovery of penicillin and its use
in staphylococcal and streptococcal infections.

Dr Ayodele Ezekiel Ogunjobi   5/09/2020 5:35:51 PM

I think RACGP should grow up. On the 7th August it was DO NOT USE HCQ. Now it is Ivermectin has insufficient evidence. I want to belief-though anyone can correct me if I am wrong- that we are doctors in this College. Many of us with qualifications in Research methodology. This epidemic of COVID is a affront to primary health system. I am yet to find a research that RACGP designed and executed either to proof or disproof HCQ or Ivermectin either as a standalone drugs or in combo with AZT, Doxycyline or Zinc. These are cheap drugs which some of us have used in the past. At least I have used HCQ and I am not psychotic yet. RACGP have joined the left who only support lock downs as the only tools of COVID control. As one learned colleagues stated, 'what have we got to loose if we try'? I have read the Lancet paper which discredited HCQ, the paper has long been withdrawn. If RACGP wants her members to be proud as doctors, let us get into the trenches and stop being on the backbench.

Dr Peter Heng Lam Chia   9/09/2020 8:49:53 PM

I agree. They are safe drugs. Evidence in medicine should be a guide and not a handcuff. Under the PBS they are non restricted drugs. If minimal inhibitory concentration is an issue then the sooner it is administered after confirmation the better. Better still use it prophylactically after known exposure.

Dr Peter Neill Hamilton-Gibbs   13/09/2020 5:10:02 PM

Although I strongly believe in evidence based medicine I feel there is a strong case to be made for medications in which there may be a positive reward/risk situation and the treatment safe. At the same time there must be continuous medical research on treatments including Ivermectin as recommended by reputable mainstream physicians. With regard to Coronavirus I am also concerned about computer modelled aggressive approach (Andrews) where the main parameter seems to be case numbers and death statistics. There seems to be no modelling on destruction of businesses and livelihood, mental health issues, delayed diagnoses of many much more serious issues, assassination of the Australian spirit with bureaucratic lockdowns and border controls. I am also concerned after 50 years in medicine the increasing leftist attitudes permeating RACGP and AMA leadership. It is particularly sad as I have always strongly supported our colleges and collegial spirit which is on a rapid decline.

Dr Stacie King   4/04/2021 10:28:37 PM

It's now 8 months since this article. Still no evidence? There's lots. Does the RACGP care to update its position statement?
It is 12 mths to the day that Monash published their in vitro study with great excitement urging for clinical trials. What have they been doing for 12/12?
The RACGP says insufficient evidence for use of Ivermectin and RCTs needed. So who is doing them?
We have "independent" "fact-checkers" (oxymoron of the century) citing a single flawed Columbian study against use of ivermectin?
Did we have RCTs for O2, steroids, monoclonal ABs, antivirals, intubation before there use?
Given current meta analyses (Hill, Lawrie), who would like to enrol their patient into an RCT with 50% chance of placebo?
How many good observational studies with pooled meta analysis is an RCT worth?
We have a gov that has threatened criminal charges against doctors prescribing off label? Has this ever occurred before in history?
To be cont....

Dr Stacie King   4/04/2021 10:52:05 PM

... cont.
Repeated lockdowns and their catastrophic effects
-increased evolutionary pressure causing rapid mutation and variants.
-total economic collapse except politics, healthcare, public service
-mental health (if not yet touched by this, probably won't be too long)
So rather than obtain the desired evidence, we have literally placed all of our eggs in the vaccine basket. (happy Easter btw).
We may have RCTs showing short term safety and efficacy of vaccines, but ironically much less evidence on immunity and long term safety than a 50c worth of ivermectin.
And in a full 12/12, the only counter argument I see are in obscure comments sections.