...In a vertiginous search for COVID-19 treatments, Caly et al conducted an in vitro exploration that showed ivermectin’s inhibitor role on the replication of the SARS-CoV-2 virus,17 18 among few other in silico and in vitro results suggesting the same.19–21 Thus, a considerable amount of preprints and protocol records quickly appeared, reporting the clinical efficacy of ivermectin in standard doses for COVID-19. The dissemination of these results caused confusion, and the general population and some clinicians endorsed the use of ivermectin, especially in Latin America.22 However, in a matter of days since the publication of Caly et al17 and its repercussions, a general publication from the Pan American Health Organization (PAHO) stated that “…ivermectin is incorrectly being used for the treatment of COVID-19, without any scientific evidence of its efficacy and safety for the treatment of this disease.”23

...Concluding, research related to ivermectin in COVID-19 has serious methodological limitations resulting in very low certainty of the evidence, and continues to grow.37–39 The use of ivermectin, among others repurposed drugs for prophylaxis or treatment for COVID-19, should be done based on trustable evidence, without conflicts of interest, with proven safety and efficacy in patient-consented, ethically approved, randomised clinical trials.

...Nevertheless, assessments of ivermectin as prophylaxis or treatment for mild to severe COVID-19 continue being published in preprints26 27and protocol repositories,28 29 which do not follow the recommended process to ensure quality stan-dards in publications; whereas peer-reviewed reports (both observational and experimental studies) are slowly emerging, yet methodologically limited by heterogeneity in population receiving ivermectin, dosis applied and uncontrolled coint-erventions.28–30 Similarly, other studies that can be rapidly retrieved in ClinicalTrials.gov, medRxiv and MEDLINE make up a quite heterogeneous body of evidence31–33 (including ivermectin as intervention, but with different underlying clin-ical questions), among other issues that do not contribute to the certainty of evidence—according to the systematic reviews that we comment on below.Up to February 2021, the PAHO identified twenty two ivermectin randomised clinical trials through a rapid review of current available liter-ature.34 There is considerable heterogeneity in the population receiving ivermectin, with studies administering it to family contacts of confirmed COVID-19 cases as a prophylactic measure29 and other studies using ivermectin for treatment of mild and moderate infected cases28 or even severe hospitalised patients.30 Applied dosis and outcomes on July 11, 2021 by guest. Protected by copyright.http://ebm.bmj.com/BMJ EBM: first published as 10.1136/bmjebm-2021-111678 on 22 April 2021. Downloaded from

...The authors claim that pooled estimates suggest beneficial effects with iver-mectin, but the certainty of the evidence was very low due to high risk of bias and small number of events throughout the included studies...

... Prospective registration of systematic reviews with or without meta-analysis protocols is a key feature for providing transparency in the review process and ensuring protection against reporting biases, by revealing differ-ences between the methods or outcomes reported in the published review and those planned in the registered protocol. These websites show pooled estimates suggesting significant benefits with ivermectin, which has resulted in confusion for clinicians, patients and even decision-makers. This is usually a problem when performing meta-analyses which are not based in rigorous systematic reviews, often leading to spread spurious or fallacious findings.36


https://ebm.bmj.com/content/ebmed/early/2021/04/21/bmjebm-2021-111678.full.pdf


Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19A Randomized Clinical Trial

Findings — In this randomized clinical trial that included 476 patients, the duration of symptoms was not significantly different for patients who received a 5-day course of ivermectin compared with placebo (median time to resolution of symptoms, 10 vs 12 days; hazard ratio for resolution of symptoms, 1.07).

Meaning — The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand effects on other clinically relevant outcomes.

Adverse Events
A total of 154 patients (77%) in the ivermectin group and 161 (81.3%) in the placebo group reported AEs between randomization and day 21. Fifteen patients (7.5%) in the ivermectin group vs 5 patients (2.5%) in the placebo group discontinued treatment due to an AE. Serious AEs developed in 4 patients, 2 in each group, but none were considered by the investigators to be related to the trial medication (Table 3; eTable 7 in Supplement 2).

Conclusions
Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.