Analgesics
Antiandrogens
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Results
Abstract
All ivermectin studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19ivm.org COVID-19 treatment researchIvermectinIvermectin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Hospitalization -211% Improvement Relative Risk Hospitalization (b) -610% Change in viral load 20% primary Change in viral load (b) 31% primary Ivermectin  COVER  EARLY TREATMENT  DB RCT Is early treatment with ivermectin beneficial for COVID-19? Double-blind RCT 61 patients in Italy (July 2020 - June 2021) Higher hospitalization (p=0.47) and improved viral clearance (p=0.59), not sig. c19ivm.org Buonfrate et al., Int. J. Antimicrobia.., Sep 2021 Favors ivermectin Favors control

High dose ivermectin for the early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof of concept trial

Buonfrate et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2021.106516 (date from preprint), COVER, NCT04438850
Sep 2021  
  Post
  Facebook
Share
  Source   PDF   All   Meta
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
Early terminated 89 patient RCT with 29 high dose and 32 very high dose ivermectin patients, showing dose dependent viral load reduction, although not reaching statistical significance due to early termination. Since most patients have low viral load at day 7, there is little room for improvement with a treatment at day 7. Intermediate results may show significantly greater improvement, but are not provided. Authors note that ivermectin remained safe even at the very high dose used, although tolerability was reduced. Adherence was very low in the very high dose arm (~60%).
The paper reports 4 SAEs, all resolved, with 3 patients hospitalized in the very high dose ivermectin arm, 1 in the high dose arm, and 0 in the control arm. However, the supplementary data is contradictory, showing 2 grade 3 events in both ivermectin arms (2 infections and infestations, and 2 COVID-19 pneumonia). While this result is not statistically significant, it may be in part due to randomization failure because three times as many patients were randomized in a hospital setting in the ivermectin arms (12/58) compared to the placebo arm (2/29), as shown in supplemental table 2, suggesting higher baseline severity in the ivermectin arms. The very high dose ivermectin arm also had more male patients (73% vs. 45%), higher median weight (79 vs. 70kg), and higher baseline cough (56% vs 42%), pyrexia (56% vs 33%), and anosmia (33% vs 17%) as per supplemental table 2.
Authors administered ivermectin on an empty stomach. Ivermectin is a lipophilic drug with low aqueous solubility and is better absorbed when given with food, especially high-fat meals. Administration with a high-fat meal can significantly increase plasma and tissue concentrations (~2.5x plasma concentration in Guzzo) and reduce time to onset of action. Standard practice for systemic use of ivermectin is administration with food (for intestinal parasitic infections, systemic distribution may not be required). Specifying fasted administration may avoid or delay the attainment of therapeutic concentrations and raises concerns about possible investigator bias.
This is the 30th of 50 COVID-19 RCTs for ivermectin, which collectively show efficacy with p=0.00000014.
This is the 62nd of 103 COVID-19 controlled studies for ivermectin, which collectively show efficacy with p<0.0000000001 (1 in 1 sextillion).
This study is excluded in the after exclusion results of meta analysis: significant unadjusted group differences, with 3 times as many patients in the ivermectin arms having the baseline visit in a hospital setting, and arm C having large differences in baseline gender, weight, cough, pyrexia, and anosmia, excessive dose for arm C.
risk of hospitalization, 210.7% higher, RR 3.11, p = 0.47, treatment 1 of 28 (3.6%), control 0 of 31 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), arm B.
risk of hospitalization, 610.0% higher, RR 7.10, p = 0.11, treatment 3 of 30 (10.0%), control 0 of 31 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), arm C, very high dose, poorly tolerated with low compliance.
relative change in viral load, RR 0.80, p = 0.59, treatment mean 2.5 (±2.2) n=28, control mean 2.0 (±4.4) n=29, day 7, arm B, primary outcome.
relative change in viral load, RR 0.69, p = 0.07, treatment mean 2.9 (±1.6) n=30, control mean 2.0 (±2.1) n=29, day 7, arm C, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Buonfrate et al., 6 Sep 2021, Double Blind Randomized Controlled Trial, Italy, peer-reviewed, 18 authors, study period 31 July, 2020 - 8 June, 2021, average treatment delay 4.0 days, dosage 1200μg/kg days 1-5, arm B 600µg/kg, arm C 1200µg/kg, trial NCT04438850 (history) (COVER).
This PaperIvermectinAll
High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial
MD Dora Buonfrate, MD Fabio Chesini, MD Davide Martini, MSc Maria Carla Roncaglioni, MSc Maria Luisa Ojeda Fernandez, MSc Maria Francesca Alvisi, MSc Irene De Simone, PhD Eliana Rulli, PhD Alessandro Nobili, MD Giacomo Casalini, Prof Spinello Antinori, PharmD Marco Gobbi, MD Caterina Campoli, PhD Michela Deiana, PhD Elena Pomari, PharmD Gianluigi Lunardi, PharmD Roberto Tessari, PhD Zeno Bisoffi
International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2021.106516
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
47 years (Q1[first quartile]-Q3[third quartile] 31.0-58.0). The majority were Europeans (97%). Comorbidities were reported by one third of the participants. Eighty (86%) participants were symptomatic with a median duration of 4 days, cough being the most frequent symptom, followed by fever and fatigue. The severity score was 1 for 78 participants (84%), and 2 for 15 (16%). Details of main physical findings, baseline laboratory exams and concomitant treatments are summarized in Supplementary Tables 3, 4 and 5. Summary of treatment compliance is reported in Table 2 . Fourteen participants (4.3%) discontinued the treatment: 1 (3.1%) in arm A, 2 (6.9%) in arm B and 11 (34.4%) in arm C. The interruptions in arm C were all due to tolerability. Seven participants received only one day of treatment, three received two and three days, respectively, and one received four days (Supplementary Table 6 ). No SADRs were observed in any of the study groups. Results on the viral load (Log10) at day 7 versus baseline, are summarized in Table 3 . In arm C, the mean reduction of the viral load was 2.9 (SD 1.6), versus 2.5 (2.2) in arm B and 2.0 (2.1) in arm A. The observed effect size (versus arm A) was 0.48 for arm C and 0.21 for arm B. Differences were not normally distributed (Shapiro-Wilk test p value <0.0001 for both comparisons), thus Wilcoxon exact test was also performed. The differences were not significant (p=0.099 and 0.122 for C versus A and B versus A, respectively). Results..
References
'hern, Sample size tables for exact single-stage phase II designs, Statistics in medicine
Agarwal, Rochwerg, Siemieniuk, Agoritsas, Lamontagne et al., A living WHO guideline on drugs for covid-19, BMJ (Clinical research ed
Baudou, Lespine, Durrieu, André, Gandia et al., Serious Ivermectin Toxicity and Human ABCB1 Nonsense Mutations, The New England journal of medicine
Bryant, Lawrie, Dowswell, Fordham, Mitchell et al., Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines, American journal of therapeutics
Buonfrate, Bisoffi, Standard Dose Ivermectin for COVID-19, Chest
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral research
Cohen, Statistical Power Analysis for the Behavioral Sciences1988
Couzin-Frankel, Antiviral pills could change pandemic's course, Science
Deiana, Mori, Piubelli, Scarso, Favarato et al., Assessment of the direct quantitation of SARS-CoV-2 by droplet digital PCR, Scientific reports
Dodd, Follmann, Wang, Koenig, Korn et al., Endpoints for randomized controlled clinical trials for COVID-19 treatments, Clinical trials
Dougan, Nirula, Azizad, Mocherla, Gottlieb et al., Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19, The New England journal of medicine
Duthaler, Suenderhauf, Karlsson, Hussner, Zu Schwabedissen et al., Population pharmacokinetics of oral ivermectin in venous plasma and dried blood spots in healthy volunteers, British journal of clinical pharmacology
Gottlieb, Nirula, Chen, Boscia, Heller et al., Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial, Jama
Gupta, Gonzalez-Rojas, Juarez, Casal, Moya et al., Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab, The New England journal of medicine
Guzzo, Furtek, Porras, Chen, Tipping et al., Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects, Journal of clinical pharmacology
Hill, Garratt, Levi, Falconer, Ellis et al., Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection, Open forum infectious diseases
Jans, Wagstaff, Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?, Cells
Jans, Wagstaff, The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?, Biochemical and biophysical research communications
Krolewiecki, Lifschitz, Moragas, Travacio, Valentini et al., Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial, EClinicalMedicine
Lawrence, Meyerowitz-Katz, Heathers, Brown, Sheldrick, The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable, Nature medicine
Lespine, Alvinerie, Sutra, Pors, Chartier, Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat, Veterinary parasitology
Lifschitz, Virkel, Sallovitz, Sutra, Galtier et al., Comparative distribution of ivermectin and doramectin to parasite location tissues in cattle, Veterinary parasitology
Mallapaty, COVID vaccines slash viral spread -but Delta is an unknown, Nature
Mega, Latin America's embrace of an unproven COVID treatment is hindering drug trials, Nature
Popp, Stegemann, Metzendorf, Gould, Kranke et al., Ivermectin for preventing and treating COVID-19, The Cochrane database of systematic reviews
Singh, Parida, Lingaraju, Kesavan, Kumar et al., Drug repurposing approach to fight COVID-19, Pharmacological reports
Smith, What constitutes success in the roll-out of COVID-19 vaccines?, Lancet
Temple, Hoang, Hendrickson, Toxic Effects from Ivermectin Use Associated with Prevention and Treatment of Covid-19, The New England journal of medicine
To, Tsang, Leung, Tam, Wu et al., Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study, The Lancet Infectious diseases
Vasudevan, Xu, Servellita, Miller, Liu et al., Digital droplet PCR accurately quantifies SARS-CoV-2 viral load from crude lysate without nucleic acid purification, Scientific reports
Zein, Sulistiyana, Raffaelo, Pranata, Ivermectin and mortality in patients with COVID-19: A systematic review, meta-analysis, and meta-regression of randomized controlled trials, Diabetes & metabolic syndrome
{ 'DOI': '10.1016/j.ijantimicag.2021.106516', 'ISSN': ['0924-8579'], 'URL': 'http://dx.doi.org/10.1016/j.ijantimicag.2021.106516', 'alternative-id': ['S0924857921013571'], 'article-number': '106516', 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-0108-6822', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Buonfrate', 'given': 'Dora', 'sequence': 'first'}, {'affiliation': [], 'family': 'Chesini', 'given': 'Fabio', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Martini', 'given': 'Davide', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Roncaglioni', 'given': 'Maria Carla', 'sequence': 'additional'}, { 'affiliation': [], 'family': 'Fernandez', 'given': 'Maria Luisa Ojeda', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Alvisi', 'given': 'Maria Francesca', 'sequence': 'additional'}, {'affiliation': [], 'family': 'De Simone', 'given': 'Irene', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0003-1058-4137', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Rulli', 'given': 'Eliana', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Nobili', 'given': 'Alessandro', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Casalini', 'given': 'Giacomo', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0003-0569-9407', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Antinori', 'given': 'Spinello', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0003-1014-6225', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Gobbi', 'given': 'Marco', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Campoli', 'given': 'Caterina', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Deiana', 'given': 'Michela', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-5182-0231', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Pomari', 'given': 'Elena', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Lunardi', 'given': 'Gianluigi', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Tessari', 'given': 'Roberto', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Bisoffi', 'given': 'Zeno', 'sequence': 'additional'}], 'container-title': ['International Journal of Antimicrobial Agents'], 'content-domain': {'crossmark-restriction': False, 'domain': []}, 'created': {'date-parts': [[2022, 1, 6]], 'date-time': '2022-01-06T16:58:51Z', 'timestamp': 1641488331000}, 'deposited': { 'date-parts': [[2022, 1, 6]], 'date-time': '2022-01-06T16:58:52Z', 'timestamp': 1641488332000}, 'indexed': {'date-parts': [[2022, 1, 6]], 'date-time': '2022-01-06T17:41:16Z', 'timestamp': 1641490876572}, 'is-referenced-by-count': 0, 'issn-type': [{'type': 'print', 'value': '0924-8579'}], 'issued': {'date-parts': [[2022, 1]]}, 'language': 'en', 'license': [ { 'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/', 'content-version': 'tdm', 'delay-in-days': 0, 'start': { 'date-parts': [[2022, 1, 1]], 'date-time': '2022-01-01T00:00:00Z', 'timestamp': 1640995200000}}, { 'URL': 'http://creativecommons.org/licenses/by-nc-nd/4.0/', 'content-version': 'vor', 'delay-in-days': 4, 'start': { 'date-parts': [[2022, 1, 5]], 'date-time': '2022-01-05T00:00:00Z', 'timestamp': 1641340800000}}], 'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S0924857921013571?httpAccept=text/xml', 'content-type': 'text/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://api.elsevier.com/content/article/PII:S0924857921013571?httpAccept=text/plain', 'content-type': 'text/plain', 'content-version': 'vor', 'intended-application': 'text-mining'}], 'member': '78', 'original-title': [], 'page': '106516', 'prefix': '10.1016', 'published': {'date-parts': [[2022, 1]]}, 'published-print': {'date-parts': [[2022, 1]]}, 'publisher': 'Elsevier BV', 'reference-count': 0, 'references-count': 0, 'relation': {}, 'score': 1, 'short-container-title': ['International Journal of Antimicrobial Agents'], 'short-title': [], 'source': 'Crossref', 'subject': ['Pharmacology (medical)', 'Infectious Diseases', 'Microbiology (medical)', 'General Medicine'], 'subtitle': [], 'title': [ 'High dose ivermectin for the early treatment of COVID-19 (COVER study): a randomised, ' 'double-blind, multicentre, phase II, dose-finding, proof of concept clinical trial'], 'type': 'journal-article'}
Loading..
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop   
Submit