Safety and Efficacy of Ivermectin for the Prevention and Treatment of COVID-19: A Double-Blinded Randomized Placebo-Controlled Study

Angkasekwinai, Nasikarn; Rattanaumpawan, Pinyo; Chayakulkeeree, Methee; Phoompoung, Pakpoom; Koomanachai, Pornpan; Chantarasut, Sorawit; Wangchinda, Walaiporn; Srinonprasert, Varalak; Thamlikitkul, Visanu

doi:10.3390/antibiotics11060796

Cited by 5 publications

(18 citation statements)

References 31 publications

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“…The characteristics of these 8 studies are presented in Table 1. [26][27][28][29][30][31][32][33] The study period of the included studies was from May 2020 to December 2021; the studies involved 165 866 participants. The COVID-19 incidence in these studies ranged from 5.2% to 73.3%.…”

Section: Resultsmentioning

confidence: 99%

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Ivermectin's Role in the Prevention of COVID‐19: A Systematic Review and Meta‐Analysis

Liang

Lin

et al. 2022

The Journal of Clinical Pharma

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This systematic review was performed to determine the population that benefited from prophylactic ivermectin. Seven databases of health-related studies were searched for eligible trials without language restrictions. Randomized controlled trials (RCTs) and cohort studies investigating ivermectin for coronavirus disease 2019 (COVID-19) prevention were included. Data were pooled using a random-effects model, and subgroups were analyzed by study type and the pre-or postexposure population. The certainty of the evidence was determined by the Grading of Recommendations Assessment, Development, and Evaluation approach. Furthermore, 4 RCTs and 4 cohort studies with a moderate to high risk of bias were included in the analysis. The prophylactic use of ivermectin significantly decreased the overall incidence of COVID-19 (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.16-0.44). Nevertheless, the positive result was not supported by the RCT. Ivermectin was associated with a lower risk of COVID-19 (OR, 0.22; 95% CI, 0.12-0.40) in the preexposure population, whereas no protective effect was observed in the postexposure population (OR, 0.39; 95% CI, 0.09-1.67). In summary, prophylactic ivermectin did not prevent COVID-19 in the postexposure population. Although the protective effect of ivermectin was shown in the overall and preexposure populations, the results were unreliable owing to poor-quality evidence.

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Section: Resultsmentioning

confidence: 99%

“…Table 2 summarizes the risk of bias for both randomized and cohort studies included in this review. [26][27][28][29][30][31][32][33] Overall, the included studies had moderate to high risks of bias. Cohen's kappa coefficient was excellent (0.83).…”

Section: Resultsmentioning

confidence: 99%

Ivermectin's Role in the Prevention of COVID‐19: A Systematic Review and Meta‐Analysis

Liang

Lin

et al. 2022

The Journal of Clinical Pharma

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“…Recent studies have also revealed the antiviral activity of ivermectin associated with the ability to inhibit flavivirus replication by targeting the NS3 helicase [ 61 ], block the importin alpha/beta-mediated nuclear transport of viral proteins, capable of inhibiting the replication of HIV-1 and dengue virus [ 62 ], and inhibit SARS-CoV-2 replication in vitro [ 63 ]. Currently, the possibility of using ivermectin for the prevention and treatment of inflammatory processes induced by viral diseases [ 8 , 9 , 10 , 11 , 12 , 13 ], as well as for the treatment of cancer patients [ 14 ], is being studied. We assumed that the therapeutic effect of ivermectin is associated not only with antiviral activity, but also with its effect on human innate immunity, namely, with its effect on neutrophil function.…”

Section: Discussionmentioning

confidence: 99%

“…Some case series analysis demonstrates the ability of ivermectin to alleviate disease-associated severity and recovery rate [ 10 , 11 ]. Another analysis failed to demonstrate the efficacy of ivermectin in the treatment of COVID-19 [ 12 , 13 ]. The therapeutic effect of ivermectin is highly dependent on the phase of the disease in which the patient receives the drug [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Ivermectin Affects Neutrophil-Induced Inflammation through Inhibition of Hydroxylysine but Stimulation of Cathepsin G and Phenylalanine Secretion

et al. 2022

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The invasion and integrin-dependent adhesion of neutrophils to lung tissues and their secretion lead to the development of pneumonia in various pulmonary pathologies, including acute respiratory distress syndrome in coronavirus disease. We studied the effect of ivermectin, a possible therapeutic agent for inflammation and cancer, on integrin-dependent neutrophil adhesion to fibronectin and the concomitant secretion. Ivermectin did not affect the attachment of neutrophils to the substrate and the reactive oxygen species production but sharply inhibited the adhesion-induced release of hydroxylysine and stimulated the release of phenylalanine and cathepsin G. Hydroxylysine is a product of lysyl hydroxylase, which is overexpressed in tumor cells with an increased ability to invade and metastasize. The inhibition of hydroxylysine release by ivermectin, by analogy, may indicate the suppression of neutrophil invasion into tissue. The increase in the release of phenylalanine in our experiments coincided with the secretion of cathepsin G, which indicates the possible role of this enzyme in the cleavage of phenylalanine. What is the substrate in such a reaction is unknown. We demonstrated that exogenously added angiotensin II (1–8) can serve as a substrate for phenylalanine cleavage. Mass spectrometry revealed the formation of angiotensin II (1–7) in the secretion of neutrophils, which attached to fibronectin in the presence of ivermectin and exogenous angiotensin II (1–8), indicating a possible involvement of ivermectin in the inactivation of angiotensin II.

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“…A double-blinded, randomized controlled trial was conducted in Thailand in 983 adults aged > 18 years with suspected COVID-19. The efficacy of a 3-day once daily dose (400–600 μg/kg/day) of ivermectin for the prevention and treatment of COVID-19 in confirmed PCR-positive cases [ 28 ]. This ivermectin should not be used for either prevention or treatment of COVID-19 in populations with a high rate of COVID-19 vaccination.…”

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confidence: 99%

Perspective: repurposed Drugs for COVID-19

2022

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IntroductionThe article aims to emphasize the necessity of proper research design, both scientifically and ethically, in order to provide good evidence for physicians to base their decisions on when prescribing drug treatment.Material and methodsResearch articles and guidelines related to therapy of COVID-19 were searched from the PubMed database.ResultsOnly remdesivir and tocilizumab are medicines that have been approved by the US FDA’s decision to approve their clinical use in moderate and severe COVID-19.ConclusionsFavipiravir, ivermectin and andrographolide need further well-conducted research to confirm the efficacy and safety against COVID-19 at different stages.

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Safety and Efficacy of Ivermectin for the Prevention and Treatment of COVID-19: A Double-Blinded Randomized Placebo-Controlled Study

Cited by 5 publications

References 31 publications

Ivermectin's Role in the Prevention of COVID‐19: A Systematic Review and Meta‐Analysis

Ivermectin's Role in the Prevention of COVID‐19: A Systematic Review and Meta‐Analysis

Ivermectin Affects Neutrophil-Induced Inflammation through Inhibition of Hydroxylysine but Stimulation of Cathepsin G and Phenylalanine Secretion

Perspective: repurposed Drugs for COVID-19

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