The Ivermectin and Covid-19 conundrum

(pic from Bharian)

So we are in the middle of a raging pandemic which has claimed over 4000 lives in Malaysia
It is natural to be worried.
We do have the tools to control the pandemic: masking, physical distancing and hand washing are still very important together with Testing and Contact tracing.  And now vaccines are being rolled out.
The approved Covid-19 vaccines in Malaysia have all been shown to be highly effective in reducing one’s risk of severe Covid-19: hospitalisation, ICU treatment and even death (this goes for the Pfizer, AztraZeneca and Sinovac/Coronovac vaccines that are currently in use in Malaysia)

Ivermectin is an old drug used to treat parasitic infections in animals (and sometimes humans) but is currently not a registered drug in Malaysia and doctors cannot legally prescribe nor pharmacies dispense the drug for human consumption. It is no surprise that the MOH has recently raided a medical practitioner for such illegal use of the drug.
In order to use or prescribe unregistered drugs, doctors in Malaysia have to get special permission from the authorities (usually in the form of compassionate use or in clinical trials).

Why are some rooting for Ivermectin as a “panacea” for this viral pandemic despite the DG of Malaysia and the official stance that there is no conclusive evidence? This is also the guidance of the WHO which states that the use of Ivermectin should only be in the context of clinical trials.  Indeed, there is one such study being embarked in Malaysia though perhaps investigators should also consider an interventional trial in earlier stages of the disease.

The evidence for Ivermectin in Covid-19 is ambigious because, as stated in the BMJ , of Misleading Clinical Evidence and Meta-analyses – this article is a good read as it explains succinctly why the evidence is weak.
There are websites which claim “evidence” by pooling together a multitude of apparently positive trials but the trouble with small poor quality trials is that it ends up with a large poor quality meta-analysis. Basically if you put together many small piles of garbage,  you get one big pile of garbage.

The authors claim that pooled estimates suggest beneficial effects with ivermectin, but the certainty of the evidence was very low due to high risk of bias and small number of events throughout the included studies. Most study results have been made publicly available as preprints or unpublished, with no peer review or formal editorial process. Others incorporated their results only in the clinical trial register, but nearly half of these randomised clinical trials had not been registered. Registering clinical trials before they begin and making results available fulfils a large number of purposes, like reducing publication and selective outcome reporting biases, promoting more efficient allocation of research funds and facilitating evidence syntheses that will inform stakeholders and decision-makers in the future.

I would also like to highlight an article by Professor Moy Foong Ming which is worth a read, in which she explains in simpler terms why there is inadequate evidence to recommend Ivermectin as prophylaxis or treatment of Covid-19 infections.

Another great blog by a “health nerd”  also worth a read,  goes into great detail and analysis on the same issue. There are some detailed explanations here on why the current evidence is of such poor quality with regard to publication bias.
It turns out that we really don’t know if ivermectin helps with Covid-19, because the evidence is mostly of such low quality that concluding anything at all is difficult.

So to those calling for wide spread use of Ivermectin in Malaysia, be warned, it could be basically another Hydroxychloroquine which as you probably know by now, ended up being more hype than hope.

Aside from the local trial, there are large ones being conducted such as the Oxford Principle study.  It is through proper study that we will learn what works and what does not. Indiscriminate use of unproven drugs should not be condoned.

So what do the majority of Malaysian doctors think? We took a straw poll in DOBBS  and 75% feel there is insufficient clinical evidence to advocate routine use, 16.5 % were unsure, and only the minority 8.5% felt there was sufficient evidence to advocate routine use.

 

Please let us know in the comments what you think.
For doctors, please do join DOBBS, Malaysia’s pioneer and largest online community for doctors. Membership is free and you can join if you haven’t by registering at https://dobbs.my/osr

In conclusion, the above implications are basically saying there is lack of good evidence for IVM in Covid-19.
There is evidence also that IVM does not work for Covid-19. See this recent paper, highlighted by a Dobber:

Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials

This analysis concluded “…in comparison to SOC or placebo, IVM did not reduce all-cause mortality, length of stay, respiratory viral clearance, adverse events and serious adverse events in RCTs of patients with mild to moderate COVID-19. We did not find data about IVM effects on clinical improvement and need for mechanical ventilation. Additional ongoing RCTs should be completed in order to update our analyses. In the meanwhile, IVM is not a viable option to treat COVID-19 patients, and only should be used within clinical trials context.”

 

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