Ivermectin for Prevention and Treatment of COVID-19 Infection

A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines

https://journals.lww.com/americanther...

Background

The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials.

A 2018 application for ivermectin use for scabies gives a direct cost of $2.90 for 100 12-mg tablets.

Most trials were registered, self-funded, and undertaken by clinicians

We assessed

Efficacy of ivermectin treatment in reducing mortality

Chemoprophylaxis

Data sources

Databases up to April 25, 2021

Sifted for studies, extracted data, and assessed risk of bias

Meta-analyses were conducted and certainty of the evidence was assessed

GRADE approach

https://training.cochrane.org/grade-a...

https://bestpractice.bmj.com/info/too...

GRADE (Grading of Recommendations, Assessment, Development and Evaluations)

Reproducible and transparent framework for grading certainty in evidence

100 organisations worldwide officially endorsing GRADE

GRADE has four levels of evidence, certainty in evidence

very low
low
moderate
high

Decreasing confidence

Risk of bias

Imprecision

Inconsistency

Indirectness

Publication bias

Increases confidence

Very large magnitude of effect

Clear dose-response gradient

Residual confounding is likely to decrease rather than increase the magnitude of effect

Data sources

24 randomized controlled trials

N = 3,406 participants

Ivermectin reduced risk of death compared with no ivermectin

Meta-analysis of 15 trials (n = 2,438)

Average risk ratio 0.38

Moderate-certainty evidence

(Confirmed using DerSimonian–Laird method and Biggerstaff–Tweedie method)

Ivermectin verses no ivermectin in hospital patients

Ivermectin, 2.3%

No ivermectin, 7.8%

Ivermectin prophylaxis reduced COVID-19 infection

3 trials, n = 738

Average reduction 86%

Low-certainty evidence

(due to study design limitations and few included trials)

Clearly favored ivermectin use

improvement

deterioration

Severe adverse events

Rare among treatment trials

Evidence of no difference was assessed as low certainty

Conclusions

Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin.

Using ivermectin early in the clinical course may reduce numbers progressing
to severe disease.

The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.

Current NIH recommendations

https://www.covid19treatmentguideline...

there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19

The sample size of most of the trials was small

Various doses and schedules of ivermectin were used

Some of the randomized controlled trials were open-label

Patients received various concomitant (confounding) medications (e.g., doxycycline, hydroxychloroquine, azithromycin, zinc, corticosteroids)

The severity of COVID-19 in the study participants was not always well described

The study outcome measures were not always clearly defined



Ivermectin for preventing and treating COVID‐19 (April, 2021)

https://www.cochranelibrary.com/cdsr/...