Current data are insufficient to determine whether the minor form or a circulating metabolite has higher direct potency against SARS-CoV-2, but it seems likely that ivermectin would need to be profoundly more potent than the reported values. Notwithstanding, ivermectin is usually present as a mixture of 2 agents and, although mainly excreted unchanged in humans, has 2 major metabolites. While ivermectin is estimated to accumulate in lung tissues (2.67 times more than plasma), this is also unlikely to be sufficient to maintain target concentrations for pulmonary antiviral activity. However, the concentrations required to inhibit viral replication in vitro (EC 50, 2.2–2.8 μM EC 90, 4.4 μM) are not achieved systemically after oral administration of the drug to humans at clinically approved doses. The antiviral activity of ivermectin has been demonstrated recently for SARS-CoV-2 in Vero/hSLAM cells. Ivermectin is a well-established antiparasitic drug used worldwide for a broad number of parasites and also for topical use against rosacea. Treatments increasing the viral clearance rate may reduce the risk of onward transmission, but this requires empirical demonstration. However, there are no approved treatments for patients with mild SARS-CoV-2 infection, either to prevent disease progression or reduce viral transmission. Preliminary data suggest that nitazoxanide and budesonide may have a role in mild infection.
#Comprehensive meta analysis cracked trial#
Other repurposed treatments such as hydroxychloroquine, lopinavir/ritonavir, remdesivir, and interferon-beta have shown no significant survival benefit in large randomized trials despite initial reports of efficacy, underscoring the need for caution when interpreting early clinical trial data.ĭexamethasone is recommended for use by the World Health Organization (WHO) and has proven survival benefits for oxygen-dependent patients with COVID-19, while tocilizumab and sarilumab improve survival for patients in intensive care. Three repurposed anti-inflammatory drugs have shown significant survival benefits to date: the corticosteroid dexamethasone in the UK RECOVERY trial and the interleukin-6 (IL-6) receptor antagonist drugs tocilizumab and sarilumab in the REMAP-CAP trial and the RECOVERY trial. The known safety profiles, shortened development timelines, and well-established markets (with low price points and higher capacity to deliver at scale) for most of the already existing compounds proposed for COVID-19 are particularly advantageous compared with new drug discovery in a pandemic situation. While research on new therapeutic agents for coronavirus disease 2019 (COVID-19) is key, there is also great interest in evaluating the potential of already existing medicines against COVID-19, and many clinical trials are in progress to “repurpose” drugs normally indicated for other diseases. Researchers worldwide are urgently looking for interventions to prevent new infections, prevent disease progression, and lessen disease severity for those already infected. Protective vaccines have been developed, but current supplies are too low to cover global demand in the coming months. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to grow, with >550 000 new infections and >9000 deaths recorded worldwide daily in July 2021. A network of large clinical trials is in progress to validate the results seen to date.ĬOVID-19, ivermectin, repurposed, SARS-CoV-2 Currently, the World Health Organization recommends the use of ivermectin only inside clinical trials. There was no significant effect of ivermectin on time to clinical recovery (mean difference, –0.57 days 95% CI, –1.31 to 0.17 P =. Ivermectin displayed a borderline significant effect on duration of hospitalization in comparison with standard of care (mean difference, –1.14 days 95% CI, –2.27 to –0.00 P =. Ivermectin did not show a statistically significant effect on survival (risk ratio, 0.90 95% CI, 0.57 to 1.42 P =. The primary meta-analysis was carried out by excluding studies at a high risk of bias. This meta-analysis investigated ivermectin in 23 randomized clinical trials (3349 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv, and trial registries. Ivermectin showed in vitro activity against SARS-COV-2, but only at high concentrations. Ivermectin is an antiparasitic drug being investigated for repurposing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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