Antiviral Effect of High-Dose Ivermectin in Adults with COVID-19: A Pilot Randomised, Controlled, Open Label, Multicentre Trial

Krolewiecki, Alejandro; Lifschitz, Adrián Luis; Moragas, Matías; Travacio, Marina; Valentini, Ricardo; Alonso, Daniel F.; Solari, Hernán G.; Ma, Tinelli; Ro, Cimino; Álvarez, Luis Ignacio Ortega; Fleitas, Pedro Emanuel; Ceballos, Laura; Golemba,; Fernández, F. M. Vega; DFd, Oliveira; Astudillo, Germán Osvaldo; Baeck, Inés; Farina, Javier; Guthmann,; Ga, Cardama; Mangano, Andrea; Spitzer, Eduardo; Gold, Silvia; Lanusse, Carlos

doi:10.2139/ssrn.3714649

Cited by 30 publications

(46 citation statements)

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“…This pilot shows a trend to lower viral loads in the ivermectin group, a trend to lower IgG titers that may re ect lesser systemic exposure to the virus and clinical bene t in cardinal symptoms of COVID-19 associated with tissue damage: anosmia/hyposmia and cough. These results are in line with emerging evidence from trials in Bangladesh 16 and Argentina 17 , as well as with recent data from a SARS-CoV-2 hamster model from Institute Pasteur which also showed a marked sex dichotomy in the effect of ivermectin on anosmia/hyposmia.…”

Section: Discussionsupporting

confidence: 90%

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with mild COVID-19: a pilot, double-blind, placebo-controlled, randomized clinical trial

Chaccour

Casellas

Matteo

et al. 2020

Preprint

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Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to determine the efficacy of a single dose of ivermectin to reduce the proportion of PCR positives, viral load at day 7 post treatment.Consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild COVID-19 (no pneumonia) and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher’s exact test and presented as a relative risk ratio.All patients recruited completed the trial (median age, 26 [range, 18-54] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0.92, 95% CI: 0.77-1.09, p = 1.0). The ivermectin group had lower median viral loads at days 4 and 7 post treatment as well as lower median IgG titers at day 21 post treatment. Hyposmia/anosmia (76 vs 158 patient-days) and cough (68 vs 97 patient-days) were less frequent in the ivermectin group.Among patients with mild COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 48 hours of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials.Trial registration ClinicalTrials.gov Identifier: NCT04390022 https://clinicaltrials.gov/ct2/show/NCT04390022

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Section: Discussionsupporting

confidence: 90%

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with mild COVID-19: a pilot, double-blind, placebo-controlled, randomized clinical trial

Chaccour

Casellas

Matteo

et al. 2020

Preprint

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“…Thirdly, in the Ahmed trial [25], ivermectin treatment for five days led to a higher percentage of patients with viral clearance at day 13 compared with one day of treatment. Finally, in Krolewiecki [31], PK/PD correlations showed significantly faster viral clearance for patients with PK exposures above 160ng/mL.…”

Section: Effects On Viral Clearancementioning

confidence: 90%

Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection

Hill

Abdulamir

Ahmed

et al. 2021

Preprint

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Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.

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“…29 Several smaller RCTs have reported no benefit with ivermectin. 30, 31, 32, 33 A trial of 585 patients concluded that combined with azithromycin, the use of nitazoxanide, ivermectin, and hydroxychloroquine led to similar clinical outcomes which were better than those in a retrospective control group of patients who had not received any of these three drugs. 34…”

Section: Introductionmentioning

confidence: 99%

Ivermectin as a potential treatment for mild to moderate COVID-19 – A double blind randomized placebo-controlled trial

Ravikirti

Roy²,

Pattadar³

et al. 2021

Preprint

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ObjectiveIvermectin has been suggested as a treatment for COVID-19.This randomised control trial was conducted to test the efficacy of Ivermectin in the treatment of mild and moderate COVID-19.DesignParallel, double blind, randomised, placebo controlled trial Setting: A tertiary care dedicated COVID-19 hospital in Bihar, IndiaParticipantsAdult patients (> 18 years) admitted with mild to moderate COVID 19 disease (saturation > 90% on room air, respiratory rate < 30 and no features of shock) with no contraindications to ivermectin and willing to participate in the studyInterventionPatients in the intervention arm were given ivermectin 12 mg on day 1 and day 2 of admission. Patients in the placebo arm were given identical looking placebo tablets. Rest of the treatment was continued as per the existing protocol and the clinical judgment of the treating teams.Outcome MeasuresThe primary outcome measure was a negative RT-PCR test for SARS-CoV-2 on day 6 of admission. The secondary outcome measures were symptom status on day 6, discharge status on day 10, admission to ICU, need for invasive mechanical ventilation and in-hospital mortality.ResultsA total of 115 patients were enrolled for the study of which 112 were included in the final analysis. Of them, 55 were randomised to the intervention arm while 57 were randomised to the placebo arm. There was no significant difference in the baseline characteristics of the two arms. There was no significant difference in the primary outcome, i.e. negative RT-PCR status on day 6 between the two groups. Similarly, there was no significant difference between the two groups in most of the secondary outcome measures, viz. symptom status on day 6, discharge status on day 10, admission to ICU, and need for invasive mechanical ventilation. However, while there was no in-hospital mortality in the intervention arm, there were 4 deaths in the placebo arm. As a result, all patients in the intervention arm (n=56) were successfully discharged as compared to 93.1% (n=54/58) in the placebo arm (RR 1.1, 95% CI 1.0 to 1.2, p=0.019).ConclusionThere was no difference in the primary outcome i.e. negative RT-PCR status on day 6 of admission with the use of ivermectin. However, a significantly higher proportion of patients were discharged alive from the hospital when they received ivermectin.Strengths and Limitations of the StudyThis study was randomised and double blind, thereby minimizing the chance of bias.All outcome measures except symptom status on day 6 were objective and placebo control was used for comparison.Only single repeat RT-PCR was done. So median time to viral clearance in the two groups could not be calculated.Severe cases were not included in the study.

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Antiviral Effect of High-Dose Ivermectin in Adults with COVID-19: A Pilot Randomised, Controlled, Open Label, Multicentre Trial

Cited by 30 publications

References 0 publications

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with mild COVID-19: a pilot, double-blind, placebo-controlled, randomized clinical trial

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with mild COVID-19: a pilot, double-blind, placebo-controlled, randomized clinical trial

Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection

Ivermectin as a potential treatment for mild to moderate COVID-19 – A double blind randomized placebo-controlled trial

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