Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients

Camprubí, Daniel; Almuedo-Riera, Alex; Martí-Soler, Helena; Soriano, Álex; Hurtado, Juan Carlos; Subirà, Carme; Grau-Pujol, Berta; Krolewiecki, Alejandro; Muñóz, José

doi:10.1371/journal.pone.0242184

Cited by 58 publications

(60 citation statements)

References 15 publications

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“…Finally, 12 studies were included in the qualitative synthesis (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), and five studies were included in the quantitative synthesis ( Figure 1). Most studies were pre-print studies and two studies (18,22) were anticipated results of clinical trials protocols.…”

Section: Selection Of Studiesmentioning

confidence: 99%

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Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis

Castañeda-Sabogal

Chambergo‐Michilot

Toro-Huamanchumo

et al. 2021

Preprint

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BackgroundTo assess the outcomes of ivermectin in ambulatory and hospitalized patients with COVID-19.MethodsFive databases and websites for preprints were searched until January 2021 for randomized controlled trials (RCTs) and retrospective cohorts assessing ivermectin versus control in ambulatory and hospitalized participants. The primary outcome was overall mortality. Secondary outcome was recovered patients. For meta-analysis, random-effects and inverse variance meta-analyses with logarithmic transformation were performed. ROBINS-I for cohort studies, and the Cochrane Risk of Bias 2.0 tool for trials were used. The strength of evidence was assessed using GRADE.ResultsAfter the selection, twelve studies (five retrospective cohort studies, six randomized clinical trials and one case series), were included. In total, 7412 participants were reported, the mean age was 47.5 (SD 9.5) years, and 4283 (58%) were male. Ivermectin was not associated with reduced mortality (logRR: 0.89, 95% CI 0.09 to 1.70, p = 0.04, I2= 84.7%), or reduced patient recovery (logRR 5.52, 95% CI -24.36 to 35.4, p = 0.51, I2 = 92.6%). All studies had a high risk of bias, and showed a very low certainty of the evidence.ConclusionsThere insufficient certainty and quality of evidence to recommend the use of ivermectin to prevent or treat ambulatory or hospitalized patients with COVID-19.

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Section: Selection Of Studiesmentioning

confidence: 99%

“…Different outcomes were evaluated by included studies, and most studies have assessed mortality and recovered patients as the primary outcome. Only four studies did not describe data regarding mortality and recovery in their analysis (14,15,22,26).…”

Section: Characteristics Of the Studies Includedmentioning

confidence: 99%

Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis

Castañeda-Sabogal

Chambergo‐Michilot

Toro-Huamanchumo

et al. 2021

Preprint

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“…Several clinical trials using IVM have been initiated either alone or in combination with other molecules 19 . IVM has already been administered to hospitalized COVID-19 patients, with contrasting outcomes: one study related no efficacy of late IVM administration (8-18 days after symptoms onset) in severe COVID-19 patients treated in combination with other drugs (hydroxychloroquine, azithromycin, tocilizumab, steroids) 20 , whereas another study observed lower mortality, especially in severe C0VID-19 patients treated with IVM in addition to usual clinical care (hydroxychloroquine, azithromycin, or both) 21 . Finally, in a pilot clinical trial, Gorial et al reported a reduction in the hospital stay for the patients receiving IVM on admission, as add-on therapy with hydroxychloroquine/azithromycin 22 .…”

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confidence: 99%

Anti-COVID-19 efficacy of ivermectin in the golden hamster

Melo

Lazarini

Larrous

et al. 2020

Preprint

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The devastating coronavirus disease 2019 (COVID-19) pandemic, due to SARS-CoV-2, has caused more than 47 million confirmed cases and more than 1.2 million human deaths around the globe1, and most of the severe cases of COVID-19 in humans are associated with neurological symptoms such as anosmia and ageusia, and uncontrolled inflammatory immune response2–5. Among therapeutic options6–8, the use of the anti-parasitic drug ivermectin (IVM), has been proposed, given its possible anti-SARS-CoV-2 activity9. Ivermectin is a positive allosteric modulator of the α-7 nicotinic acetylcholine receptor10, which has been suggested to represent a target for the control of Covid-19 infection11, with a potential immunomodulatory activity12. We assessed the effects of IVM in SARS-CoV-2-intranasally-inoculated golden Syrian hamsters. Even though ivermectin had no effect on viral load, SARS-Cov-2-associated pathology was greatly attenuated. IVM had a sex-dependent and compartmentalized immunomodulatory effect, preventing clinical deterioration and reducing olfactory deficit in infected animals. Importantly, ivermectin dramatically reduced the Il-6/Il-10 ratio in lung tissue, which likely accounts for the more favorable clinical presentation in treated animals. Our data support IVM as a promising anti-COVID-19 drug candidate.

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“… 81 Other small, non-randomized trials , which are potentially biased, have reported conflicting results regarding the benefit of ivermectin. 82–84 …”

Section: Resultsmentioning

confidence: 99%

From hydroxychloroquine to ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2?

Rakedzon

Neuberger

Domb

et al. 2021

Journal of Travel Medicine

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Background: Nearly a year into the COVID-19 pandemic we still lack effective anti SARS-CoV-2 drugs with substantial impact on mortality rates except for dexamethasone. As the search for effective antiviral agents continues, we aimed to review data on the potential of repurposing antiparasitic drugs against viruses in general, with an emphasis on coronaviruses. Methods: We performed a review by screening in vitro and in vivo studies that assessed the antiviral activity of several antiparasitic agents: chloroquine, hydroxychloroquine, mefloquine, artesiminins, ivermectin, nitazoxanide, niclosamide, atovaquone, and albendazole. Results: For hydroxychloroquine and chloroquine we found ample in vitro evidence of antiviral activity. Cohort studies that assessed the use of hydroxychloroquine for COVID-19 reported conflicting results, but randomized controlled trials (RCTs) demonstrated no effect on mortality rates and no substantial clinical benefits of HCQ (hydroxychloroquine) used either for prevention or treatment of COVID-19. We found two clinical studies of artesiminins and two studies of nitazoxanide for treatment of viruses other than COVID-19, all of which showed mixed results. Ivermectin was evaluated in one RCT and few observational studies, demonstrating conflicting results. As the level of evidence of these data is low, the efficacy of ivermectin against COVID-19 remains to be proven. For chloroquine, hydroxychloroquine, mefloquine, artesiminins, ivermectin, nitazoxanide and niclosamide we found in vitro studies showing some effects against a wide array of viruses. We found no relevant studies for atovaquone and albendazole. Conclusions: As the search for an effective drug active against SARS-CoV-2 continues, we argue that pre-clinical research of possible antiviral effects of compounds that could have antiviral activity should be conducted. Clinical studies should be conducted when sufficient in vitro evidence exists, and drugs should be introduced into widespread clinical use only after being rigorously tested in RCTs. Such a search may prove beneficial in this pandemic, or in outbreaks yet to come.

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Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients

Cited by 58 publications

References 15 publications

Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis

Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis

Anti-COVID-19 efficacy of ivermectin in the golden hamster

From hydroxychloroquine to ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2?

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