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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Ventilation 40% Improvement Relative Risk ICU admission 33% Improvement at day 8 -33% Viral clearance -25% primary Ivermectin  Camprubí et al.  LATE TREATMENT Is late treatment with ivermectin beneficial for COVID-19? Retrospective 26 patients in Spain Study underpowered to detect differences c19ivm.org Camprubí et al., PLoS ONE, November 2020 Favors ivermectin Favors control

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

Camprubí et al., PLoS ONE, 15:11, doi:10.1371/journal.pone.0242184
Nov 2020  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 103 studies, recognized in 22 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19ivm.org
Tiny 26 patient retrospective study of very late treatment with ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses. All patients received HCQ which may reduce the potential benefit for adding ivermectin.
Although the 40% lower ventilation is not statistically significant, it is consistent with the significant 35% lower ventilation [17‑50%] from meta analysis of the 20 ventilation results to date.
Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.
This is the 18th of 103 COVID-19 controlled studies for ivermectin, which collectively show efficacy with p<0.0000000001 (1 in 1 sextillion).
50 studies are RCTs, which show efficacy with p=0.00000014.
risk of mechanical ventilation, 40.0% lower, RR 0.60, p = 0.67, treatment 3 of 13 (23.1%), control 5 of 13 (38.5%), NNT 6.5.
risk of ICU admission, 33.3% lower, RR 0.67, p = 1.00, treatment 2 of 13 (15.4%), control 3 of 13 (23.1%), NNT 13, ICU at day 8.
risk of no improvement at day 8, 33.3% higher, RR 1.33, p = 1.00, treatment 4 of 13 (30.8%), control 3 of 13 (23.1%).
risk of no viral clearance, 25.0% higher, RR 1.25, p = 1.00, treatment 5 of 13 (38.5%), control 4 of 13 (30.8%), tests done between days 3-5, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Camprubí et al., 11 Nov 2020, retrospective, Spain, peer-reviewed, 9 authors, average treatment delay 12.0 days, dosage 200μg/kg single dose.
This PaperIvermectinAll
Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients
Daniel Camprubí, Alex Almuedo-Riera, Helena Martí-Soler, Alex Soriano, Juan Carlos Hurtado, Carme Subirà, Berta Grau-Pujol, Alejandro Krolewiecki, Jose Muñoz
PLOS ONE, doi:10.1371/journal.pone.0242184
Ivermectin has recently shown efficacy against SARS-CoV-2 in-vitro. We retrospectively reviewed severe COVID-19 patients receiving standard doses of ivermectin and we compared clinical and microbiological outcomes with a similar group of patients not receiving ivermectin. No differences were found between groups. We recommend the evaluation of high-doses of ivermectin in randomized trials against SARS-CoV-2.
Author Contributions Conceptualization: Daniel Camprubı ´, Alex Almuedo-Riera, Alejandro Krolewiecki, Jose Muñoz. Data curation: Juan Carlos Hurtado, Carme Subirà. Formal analysis: Daniel Camprubı ´, Helena Martı ´-Soler. Investigation: Juan Carlos Hurtado, Jose Muñoz. Methodology: Daniel Camprubı ´, Alex Almuedo-Riera, Jose Muñoz. Writing -original draft: Daniel Camprubı ´, Jose Muñoz. Writing -review & editing: Alex Almuedo-Riera, Helena Martı ´-Soler, Alex Soriano, Carme Subirà, Berta Grau-Pujol, Alejandro Krolewiecki, Jose Muñoz.
References
Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19-preliminary report, New Engl J Med, doi:10.1056/NEJMoa2007764
Buonfrate, Salas-Coronas, Muñoz, Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial, Lancet Infect Dis, doi:10.1016/S1473-3099%2819%2930289-0
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104787
Chaccour, Hamman, Ramo ´n-Garcı ´a, Rabinovich, Ivermectin and Novel Coronavirus Disease (COVID-19): Keeping Rigor in Times of Urgency, Am J Trop Med Hyg
Guzzo, Furtek, Porras, Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects, J Clin Pharmacol, doi:10.1177/009127002401382731
Kamgno, Gardon, Gardon-Wendel, Adverse systemic reactions to treatment of onchocerciasiswith ivermectin at normal and high doses given annually or three-monthly, Trans R Soc TropMed Hyg, doi:10.1016/j.trstmh.2003.10.018
Momekov, Momekova, Ivermectin as a potential COVID-19 treatment from a pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens, Biotechnology & Biotechnological Equipment, doi:10.1080/13102818.2020.1775118
Muñoz, Ballester, Antonijoan, Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers, PLoS Negl Trop Dis, doi:10.1371/journal.pntd.0006020
Navarro, Camprubı, ´ndez, Safety of high-dose ivermectin: a systematic review and meta-analysis, J Antimicrob Chemother, doi:10.1093/jac/dkz524
Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic Treatments for Coronavirus Disease, A Review, doi:10.1001/jama.2020.6019
Smit, Ochomo, Aljayyoussi, Human Direct Skin Feeding Versus Membrane Feeding to Assess the Mosquitocidal Efficacy of High-Dose Ivermectin (IVERMAL Trial), Clin Infect Dis, doi:10.1093/cid/ciy1063
The, Group, Dexamethasone in Hospitalized Patients with Covid-19-Preliminary Report, New Engl J Med, doi:10.1056/NEJMoa2021436
Wimmersberger, Coulibaly, Schulz, Efficacy and safety of ivermectin against Trichuris trichiura in preschool-aged and school-aged children: a randomized controlled dose-finding trial, Clin Infect Dis, doi:10.1093/cid/ciy246
´ndez, Buonfrate, Gomez-Junyent, Zammarchi, Bisoffi et al., Evidence-Based Guidelines for Screening and Management of Strongyloidiasis in Non-Endemic Countries, Am J Trop Med Hyg, doi:10.4269/ajtmh.16-0923
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Late treatment
is less effective
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