Use of ivermectin in the treatment of Covid-19: a pilot trial

Pott-Junior et al., Toxicology Reports, doi:10.1016/j.toxrep.2021.03.003, NCT04431466

Mar 2021

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Very small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe and reduces symptoms and viral load, and that the antiviral effect appears to be dose-dependent. NCT04431466 (history).

Retraction/censorship: this paper appears to have been censored at the request of the journal's founding editor pubmed.ncbi.nlm.nih.gov. An external review is mentioned but is not provided, and there is no reply from the authors, or indication that the authors were notified. Conclusions in this study are limited due to the small size, however we should consider all information in the context of the full body of research.

Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.

This is the 20th of 46 COVID-19 RCTs for ivermectin, which collectively show efficacy with p=0.00000014.

This is the 42nd of 99 COVID-19 controlled studies for ivermectin, which collectively show efficacy with p<0.0000000001 (1 in 2 sextillion).

1. Porter et al., The ratio between SARS-CoV-2 RNA viral load and culturable viral titer differs depending on stage of infection, medRxiv, doi:10.1101/2023.07.06.23292300.medrxiv.org, doi.org.

2. pubmed.ncbi.nlm.nih.gov, pubmed.ncbi.nlm.nih.gov/35528725/.pubmed.ncbi.nlm.nih.gov/35528725/.

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risk of mechanical ventilation, 85.2% lower, RR 0.15, p = 0.25, treatment 1 of 27 (3.7%), control 1 of 4 (25.0%), NNT 4.7.

risk of ICU admission, 85.2% lower, RR 0.15, p = 0.25, treatment 1 of 27 (3.7%), control 1 of 4 (25.0%), NNT 4.7.

relative improvement in Ct value, 0.8% better, RR 0.99, p = 1.00, treatment 27, control 3.

risk of no viral clearance, 11.1% higher, RR 1.11, p = 1.00, treatment 10 of 27 (37.0%), control 1 of 3 (33.3%), primary outcome.

time to viral-, 16.7% lower, relative time 0.83, treatment 27, control 3.

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Pott-Junior et al., 9 Mar 2021, Randomized Controlled Trial, Brazil, peer-reviewed, 10 authors, study period 1 July, 2020 - 1 December, 2020, average treatment delay 8.0 days, dosage 200μg/kg single dose, dose varies in three arms 100, 200, 400μg/kg, trial NCT04431466 (history).

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RETRACTED: Use of ivermectin in the treatment of Covid-19: A pilot trial

Henrique Pott-Junior, Mˆonica Maria Bastos Paoliello, Alice De Queiroz Constantino Miguel, Anderson Ferreira Da Cunha, Caio Cesar De Melo Freire, F´abio Fernandes Neves, Lucimar Retto Da Silva De Av´o, Meliza Goi Roscani, Sigrid De Sousa Dos Santos, Silvana Gama Florêncio Chach´a

Toxicology Reports, doi:10.1016/j.toxrep.2021.03.003

In this randomized open-label trial pilot study we assessed the antiviral effects and safety of various doses of ivermectin in patients with mild clinical symptoms of COVID-19. Methods: Patients were randomly assigned to receive standard of care (SOC) treatment at hospital admission; SOC plus ivermectin 100 mcg/kg; SOC plus ivermectin 200 mcg/kg; or SOC plus ivermectin 400 mcg/kg. The primary assessed endpoint was the proportion of patients who achieved two consecutive negative SARS-CoV-2 RT PCR tests within 7 days of the start of the dosing period. This study was registered at ClinicalTrials.gov (NCT04431466). Results: A total of 32 patients were enrolled and randomized to treatment. SOC treatment together with ivermectin did not result in any serious adverse events. All patients exhibited a reduction in SARS-CoV-2 viral load within 7 days; however, those who received ivermectin had a more consistent decrease as compared to the SOC alone group, characterized by a shorter time for obtaining two consecutive negative SARS-CoV-2 RT PCR tests. Conclusions: Ivermectin is safe in patients with SARS-CoV-2, reducing symptomatology and the SARS-CoV-2 viral load. This antiviral effect appears to depend on the dose used, and if confirmed in future studies, it suggests that ivermectin may be a useful adjuvant to the SOC treatment in patients with mild COVID-19 symptoms.

CRediT authorship contribution statement Henrique Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Late treatment
is less effective

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