Abstract Objectives 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.
Ivermectin is a well-known antiparasitic, highly effective against helminthic infestations and with an excellent safety profile. In the past few years, studies have shown that ivermectin also has an antiviral effect on DNA and RNA viral families, preventing the virus from entering cells; promoting inhibition of the transporter complex "nuclear transporter mediated by α / β importin", fundamental to the viral replication process; and binding to RNA-dependent RNA polymerases, also leading to disruption of viral replication [, , , ].
Countries where the use of ivermectin against parasitic infections is common, such as in Africa, have significantly lower incidence of COVID-19. More recently, ivermectin’s antiviral effect was tested in vitro in Vero/hSLAM cells infected with SARS-CoV-2 (isolate Australia/VIC01/2020) ]. After 48 h, there was a 5000-fold reduction in viral RNA in ivermectin-treated samples as compared to controls. Although these findings highlighted the potential use of ivermectin as an antiviral drug in the fight against COVID-19, the dose used was 200 times greater than those commonly used in clinical indications .
Nevertheless, the negative impact of COVID-19 global pandemic and the urgent demand for an efficacious, safe, and widely available treatment for the disease has led to a widely spread prescription of ivermectin as a treatment option for SARS-CoV-2 infection. However, the information on the anti-SARS-CoV-2 activity of ivermectin in vivo is scarce. Thus, the primary objective of the present study was to assess the antiviral effects and safety of different doses of ivermectin in patients with mild COVID-19 symptoms.
ARS-CoV-2 viral load measurements
SARS-CoV-2 RT-PCR and cycle thresholds were performed according to the guidelines set forth by the US Centers for Disease Control and Prevention (CDC) . Undetectable viral load was defined as two consecutive non-detectable SARS-CoV-2 RT-PCR tests. All patients collected daily nasopharyngeal swab specimens until reaching undetectable viral load or completing 7 days of evaluation. Investigators and patients were blinded to the viral load results during the study dosing period.
3.1. Patient characteristics
Thirty-two patients were enrolled in the study, one dropped out prior to receiving medication, and one was excluded from the Per Protocol (PP) analysis due to protocol violation (Fig. 1). Baseline characteristics are presented in Table 1.
Although the present study is preliminary, the results suggest that administration of ivermectin in patients with SARS-CoV-2 is safe, reducing symptomatology and viral load, thus providing evidence for the potential benefit of early intervention with this drug. Ivermectin’s antiviral effects appear to depend on the administered dose. A larger randomized controlled clinical trial of ivermectin treatment is warranted to validate these important findings. The outbreak of coronavirus disease presents enormous challenges for health, social and economic systems worldwide. If the results of this pilot trial could be further confirmed, ivermectin may be a useful adjuvant to the standard of care treatment for patients with COVID-19, providing a safe and economic tool for coping with the disease.
Credited to HenriquePott-Junior