Ivermectin: Inconclusive Evidence

Ivermectin has been garnering tremendous interest. A google search trend shows that “Ivermectin” google searches have increased in Malaysia since May 2021, and its interest has been peaking as of the time of writing.1 Much has been said by various groups on its use; news reports reflect the public dilemma towards Ivermectin. It seems Ivermectin in its current state has become synonymous with controversy. 

Editor’s Note: CARiNG Pharmacy Does Not Sell Ivermectin

First off, the writer would like to clarify that this drug is currently not available at any of our CARiNG Pharmacy stores. We supply medicines approved by the Ministry of Health Malaysia. We encourage all medication taken only under medical supervision. 

The Status of Ivermectin in Malaysia

Ivermectin has not been approved by the MOH for use in the treatment or prevention of COVID-19. A search in the National Pharmaceutical Regulatory Agency (NPRA) showed various ivermectin formulations are approved for use in veterinary medicine (animals such as dogs, cats, farm animals, etc).2 

In view of the high interest the public have on its use in COVID-19, the MOH and the Institute for Clinical Research (ICR) have initiated a multicentre open-label randomized controlled trial – The Ivermectin Treatment Efficacy in COVID-19 High Risk Patients (I-TECH Study) will be conducted in 12 MOH hospitals. The study is expected to be completed in September 2021 and will provide more clarity on its usage.3   

Ministry of Health Released a Ivermectin Evidence Update on July 2021

A rapid review was released by the MOH which reviewed the available evidence on Ivermectin and its effectiveness and safety when used in treatment of COVID-19.4 It is a 13 page long document, therefore the writer will attempt to summarise it to a few important points.

Effectiveness & Safety:

  • Positive Effectiveness Findings: A trial by Khan et al. (2020) (Bangladesh) that had positive findings such as lower hospitalisation, lower use of oxygen supplementation, shorter length of hospitalisation and lower death rates for those treated by Ivermectin.5 Kim et al. (2020) (Korea) reviewed 10 trials that found Ivermectin reduced death rates in critically ill COVID-19 patients treated with Ivermectin.6  
  • Inconclusive Effectiveness Findings: A review by Castañeda-Sabogal et al (2021) (Peru) reviewed 12 trials and found no reduction in the death rates or recovery rates for those treated with Ivermectin.7 The review by Bartoszko et (2021) (Canada & others) also found inconclusive evidence in improvements of death rate, recovery rate, hospitalisation when Ivermectin was used.8 
  • Positive Safety Findings. The trial by Galan et al (2021) (Brazil) studied safety and efficacy of Ivermectin, chloroquine (CQ) and hydroxychloroquine (HCQ) used in severe forms of COVID-19. The safety profile of all three were favourable, meaning Ivermectin was safe to use. However the same study showed that all three drugs did not show positive effectiveness in COVID-19 treatment.9 
  • Negative Safety Findings. The trial by Okomus et al (2021) (Indonesia) observed side effects such as nausea, vomiting and liver damage in people treated with Ivermectin.10 A review by Bryant et al. (2021) (UK) observed Ivermectin was associated with side effects such as hyponatremia (low sodium levels) and delirium.11

Poor Quality of Evidence

  • Many trials that showed positive findings were of “low quality”, i.e. some had very few subjects and some trials were not adjusted for confounding factors. 
  • Confounding factors were noted in some trials. This error can occur when for example drug X was used together with Ivermectin. A positive outcome was seen on a patient, but it cannot be ascertained the outcome was a result from treatment with drug X or with Ivermectin.
  • Some of the systematic reviews were pre-printed articles. For example Karale et al. (2021) (India, US) showed positive findings12, however it was not peer-reviewed. 
  • A preprint is a full draft research paper that is shared publicly before it has been peer reviewed. In other words, the research has not been scrutinised closely by other experts in the field – this is another example of low quality evidence.
  • In the academic field, certain trials are “powered” or specifically designed to study the side effects of a drug. There was a lack of high quality reviews on the safety of Ivermectin treatment.

Other Notable Reviews

  • There were no studies available to identify the cost effectiveness in using Ivermectin as a treatment or prevention of COVID-19. 
  • Cost effective analysis is important for decision makers to to know if an intervention is cost saving, and if not how much more would it cost to implement it compared to a less effective intervention.13

Take Away Message: We Need More Evidence

It is easy to be persuaded by “personal testimonies” and hearsays. However, as explained, even the scientific evidence available has not been resolute in claiming Ivermectin as safe and effective. As we wait with baited breath on the findings of MOH when it comes to the use of Ivermectin in COVID-19, let’s trust the health authorities and let them treat COVID-19 cases in accordance with evidence based international treatment guidelines. 

Conclusion: Let’s Get Vaccinated

As exemplified by various countries, high vaccination rates reduce the risk of hospitalisation and death from COVID-19. It is imperative that all healthy adults receive a Covid-19 vaccine to protect ourselves and the people around us. Let’s play our part and get vaccinated against COVID-19.

#LindungDiriLindungSemua

*Article reviewed on 3 Aug 2021.

References:

  1. Google Trend “Ivermectin”. (Web accessed August 2021) Weblink: https://trends.google.com/trends/explore?q=ivermectin&geo=MY
  2. Quest. NPRA. “Search: Active Ingredient: Ivermectin”. (Web accessed August 2021) Web link:  https://www.npra.gov.my/index.php/en/consumers/information/products-search
  3. Ministry of Health Malaysia starts Ivermectin trial for high risk COVID-19 patients (I-TECH Study). DG of Health. (5 June 2021). Web link: https://kpkesihatan.com/2021/06/05/ministry-of-health-malaysia-starts-ivermectin-trial-for-high-risk-covid-19-patients-i-tech-study/
  4. Mahtas Covid-19 Rapid Evidence Updates. Ivermectin for Treatment of Covid-19. Based on available evidence up till (2 July 2021) https://covid-19.moh.gov.my/kajian-dan-penyelidikan/mahtas-covid-19-rapid-evidence-updates/15_Rapid_Review_Ivermectin_16072021.pdf
  5. Khan MSI, Debnath CR, Nath PN, et al. Ivermectin Treatment May Improve the Prognosis of Patients With COVID-19. Arch Bronconeumol. 2020;56(12):828–30.
  6. Kim MS, An MH, Kim WJ, Hwang TH. Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis. Kretzschmar MEE, editor. PLOS Med. 2020;17(12):e1003501. Available from: https://dx.plos.org/10.1371/journal.pmed.1003501
  7. Castañeda-Sabogal A, Chambergo-Michilot D, Toro-Huamanchumo CJ, et al. Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and metaanalysis. medRxiv. 2021;2021.01.26.21250420. Available from: https://www.medrxiv.org/content/10.1101/2021.01.26.21250420v1
  8. Bartoszko JJ, Siemieniuk RAC, Kum E et al. Prophylaxis against covid-19: Living systematic review and network meta-analysis. BMJ [No date]. 2021;373:1–12.
  9. Galan LEB, Santos NM, Asato MS, et al. Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalised patients with severe manifestations of SARS-CoV-2 infection. Pathog Glob Health. 2021;115(4):235–42. Available from: https://doi.org/10.1080/20477724.2021.1890887
  10. Okumuş N, Demirtürk N, Çetinkaya RA, et al. Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients. BMC Infect Dis 2021;21(1):1–11.
  11. Bryant A, Lawrie TA, Dowswell T, et al. Ivermectin for Prevention and Treatment of COVID-19 Infection. Am J Ther. 2021; Available from: https://journals.lww.com/10.1097/MJT.0000000000001402
  12. Karale S, Bansal V, Makadia J, et al. A meta-analysis of mortality, need for ICU admission, use of mechanical ventilation and adverse effects with ivermectin use in COVID-19 patients. medRxiv. 2021;2021.04.30.21256415. Available from: https://doi.org/10.1101/2021.04.30.21256415
  13. Cost-Effectiveness Analysis (CDC) (Web accessed August 2021) Weblink: https://www.cdc.gov/policy/polaris/economics/cost-effectiveness/index.html