Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines
You can find the full paper embedded below (the embed has a link to Google PDF viewer too)
From the abstract:
Therapeutic Advances: Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin {...} Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%–91%)...
This is an important and significant study because of its depth and scope and focus upon only RCT studies (i.e. the higher quality randomized control trial type).
Here are a few of the paragraphs I found most useful in terms of gaining an overview of what the paper/study reports:
Introduction:
Since the start of the SARS-CoV-2 pandemic, both observational and randomized studies have evaluated ivermectin as a treatment for, and as prophylaxis against, COVID-19 infection. A review by the Front Line COVID-19 Critical Care Alliance summarized findings from 27 studies on the effects of ivermectin for the prevention and treatment of COVID-19 infection, concluding that ivermectin “demonstrates a strong signal of therapeutic efficacy” against COVID19.9 Another recent review found that ivermectin reduced deaths by 75%.10 Despite these findings, the National Institutes of Health in the United States recently stated that “there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19,”11 and the World Health Organization recommends against its use outside ofclinical trials.1
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Developing new medications can take years; therefore, identifying existing drugs that can be repurposed against COVID-19 that already have an established safety profile through decades of use could play a critical role in suppressing or even ending the SARS-CoV2 pandemic. Using repurposed medications may be especially important because it could take months, possibly years, for much of the world’s population to get vaccinated, particularly among LMIC populations. Currently, ivermectin is commercially available and affordable in many countries globally.6 A 2018 application for ivermectin use for scabies gives a direct cost of $2.90 for 100 12-mg tablets.22 A recent estimate from Bangladesh23 reports a cost of US$0.60—US$1.80 for a 5-day course of ivermectin. For these reasons, the exploration of ivermectin’s potential effectiveness against SARS-CoV-2 may be of particular importance for settings with limited resources.24 If demonstrated to be effective as a treatment for COVID-19, the costeffectiveness of ivermectin should be considered against existing treatments and prophylaxes. The aim of this review was to assess the efficacy of ivermectin treatment among people with COVID-19 infection and as a prophylaxis among people at higher risk of COVID-19 infection. In addition, we aimed to prepare a brief economic commentary (BEC) of ivermectin as treatment and as prophylaxis for COVID-19.25
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Discussion:
The findings indicate with moderate certainty that ivermectin treatment in COVID-19 provides a significant survival benefit. Our certainty of evidence judgment was consolidated by the results of trial sequential analyses, which show that the required IS has probably already been met. Low-certainty evidence on improvement and deterioration also support a likely clinical benefit of ivermectin. Low-certainty evidence suggests a significant effect in prophylaxis. Overall, the evidence also suggests that early use of ivermectin may reduce morbidity and mortality from COVID-19. This is based on (1) reductions in COVID-19 infections when ivermectin was used as prophylaxis, (2) the more favorable effect estimates for mild to moderate disease compared with severe disease for death due to any cause, and (3) on the evidence demonstrating reductions in deterioration.
The evidence on severe adverse events in this review was graded as low certainty, partly because there were too few events to reach statistical significance. Evidence from a recent systematic review of ivermectin use among people with parasitic infections suggests that ivermectin administered at the usual doses (0.2 or 0.4 mg/kg) is safe and could be safe at higher doses.7,116 A recent World Health Organization document on ivermectin use for scabies found that adverse events with ivermectin were primarily minor and transient.22 We restricted the included studies to the highest level of evidence, that is, RCTs, as a policy. This was despite there being numerous observational but nonrandomized trials of ivermectin, which one could argue could also be considered in an emergency. We included preprint and unpublished data from completed but not yet published trials due to the urgency related to evidence synthesis in the context of a global pandemic.117 Although there is the potential for selective reporting of outcomes and publication bias, we have factored in these considerations in interpreting results and forming conclusions. We adhered to PRISMA guidelines and the WHO statement on developing global norms for sharing data and results during public health emergencies.117
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RCTs in this review did not specifically examine use of ivermectin in the elderly, although this is a known high-risk group for severe COVID-19. In the setting of care homes, it is also notorious for rapid contagion. A standard indication for ivermectin in the elderly is scabies. We identified 2 recent reports suggesting that ivermectin may be efficacious as prevention and treatment of COVID-19 in this age group.50,127 A letter on positive experience in 7 elder care facilities in Virginia covering 309 patients was sent to NIH127 and has recently been submitted for publication.
There is also evidence emerging from countries where ivermectin has been implemented. For example, Peru had a very high death toll from COVID-19 early on in the pandemic.128 Based on observational evidence, the Peruvian government approved ivermectin for use against COVID-19 in May 2020.128 After implementation, death rates in 8 states were reduced between 64% and
91% over a two-month period.128 Another analysis of Peruvian data from 24 states with early ivermectin deployment has reported a drop in excess deaths of 59% at 30+ days and of 75% at 45+ days.129 However, factors such as change in behavior, social distancing, and face-mask use could have played a role in this reduction. Other considerations related to the use of ivermectin
treatment in the COVID-19 pandemic include people’s values and preferences, equity implications, acceptability, and feasibility.130 None of the identified reviews specifically discussed these criteria in relation to ivermectin. However, in health care decision making, evidence on effectiveness is seldom taken in isolation without considering these factors. Ultimately, if ivermectin is to be more widespread in its implementation, then some considerations are needed related to these decision-making criteria specified in the GRADE-DECIDE framework.130...
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Given the evidence of efficacy, safety, low cost, and current death rates, ivermectin is likely to have an impact on health and economic outcomes of the pandemic across many countries. Ivermectin is not a new and experimental drug with an unknown safety profile. It is a WHO “Essential Medicine” already used in several different indications, in colossal cumulative volumes. Corticosteroids have become an accepted standard of care in COVID-19, based on a single RCT of dexamethasone.1 If a single RCT is sufficient for the adoption of dexamethasone, then a fortiori the evidence
of 2 dozen RCTs supports the adoption of ivermectin. Ivermectin is likely to be an equitable, acceptable, and feasible global intervention against COVID-19. Health professionals should strongly consider its use, in both treatment and prophylaxis.
