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Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease

Bukhari et al., medRxiv, doi:10.1101/2021.02.02.21250840 (results 1/16), NCT04392713
Jan 2021  
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Viral clearance 82% primary Improvement Relative Risk Viral clearance (b) 39% Ivermectin  Bukhari et al.  EARLY TREATMENT  RCT Is early treatment with ivermectin beneficial for COVID-19? RCT 86 patients in Pakistan (March - June 2020) Improved viral clearance with ivermectin (p=0.0000081) c19ivm.org Bukhari et al., medRxiv, January 2021 Favorsivermectin Favorscontrol 0 0.5 1 1.5 2+
Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020, now with p < 0.00000000001 from 105 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19ivm.org
RCT of relatively low risk hospitalized patients with 50 ivermectin and 50 control patients showing significantly faster viral clearance with treatment. 9 patients in the treatment arm were lost to followup compared with 5 in the control arm, which could be in part due to faster recovery with treatment. There were no safety concerns. No mortality was reported. The numbers in Table 3 are the number of patients that became negative on that day, i.e., non-cumulative. SOC included vitamin C and vitamin D. NCT04392713 (history).
This is the 14th of 52 COVID-19 RCTs for ivermectin, which collectively show efficacy with p=0.00000021.
This is the 33rd of 105 COVID-19 controlled studies for ivermectin, which collectively show efficacy with p<0.0000000001 (1 in 774 quintillion).
risk of no viral clearance, 82.4% lower, RR 0.18, p < 0.001, treatment 4 of 41 (9.8%), control 25 of 45 (55.6%), NNT 2.2, day 7, primary outcome.
risk of no viral clearance, 38.7% lower, RR 0.61, p < 0.001, treatment 24 of 41 (58.5%), control 43 of 45 (95.6%), NNT 2.7, day 3.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Bukhari et al., 16 Jan 2021, Randomized Controlled Trial, Pakistan, preprint, 10 authors, study period 15 March, 2020 - 15 June, 2020, dosage 12mg single dose, trial NCT04392713 (history).
This PaperIvermectinAll
Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease
Karamat Hussain Shah Bukhari, Dr Asma Asghar, Najma Perveen, Dr Arshad Hayat, Dr Sermad Ahmad Mangat, Kamil Rehman Butt, Dr Mohammad Abdullah, Tehreem Fatima, Ahmad Mustafa, Talal Iqbal
doi:10.1101/2021.02.02.21250840
Objective: To evaluate the efficacy of ivermectin (IVM) as an addition to the standard of care (SOC) treatment in COVID-19 patients with mild and moderate disease Materials and Methods: A randomized clinical trial (Trial registration # NCT04392713) was carried out at Combined Military Hospital Lahore from March 15, 2020, to June 15, 2020. Eighty-six patients with reverse transcriptase-polymerase chain reaction (RT-PCR) proven SARS-CoV-2 infection completed the trial protocol. Patients were stratified via the lottery method into two groups. Group A was administered standard of care (SOC) treatment as per existing hospital guidelines whereas group B was given ivermectin (single dose of 12 milligrams) along with SOC treatment. PCR was repeated at 72 hours, 7 th day, and at 14 th day of admission for both the groups and the point at which the PCR became negative was noted. Complete blood counts, liver function tests and renal function tests were done at recruitment, 7 th day, and 14 th day. The primary outcome was the viral clearance, measured as days to achieve PCR negativity. The secondary outcome was the development of any adverse side effects pertinent to ivermectin or derangement in baseline laboratory parameters. Results: In group A, 36 (80%) participants were males, and 9 (20%) were females, whereas in group B, 37 (90.2%) were males and 4 (9.8%) were females. Mean age was 39.0 ± 12.6 and 42.2 ± 12.0 years for groups A and B, respectively (p= 0.394). There was early viral clearance in group B as compared to group A (p=0.001). No adverse reaction or derangements in laboratory parameters was noted in the intervention arm during the trial period.
Declarations Ethical approval and consent to participate -the approval was sought from Combined Military Hospital Lahore Ethics Review Board (ERC # 169/2020) and the trial was registered before initiation (Trial registration # NCT04392713). Consent for publication -not applicable Competing interests -The authors declare that they have no competing interests. Funding -not applicable
References
Banerjee, Nandy, Dalai, Ahmed, The Battle against COVID 19 Pandemic: What we Need to Know Before we "Test Fire" Ivermectin, Drug Res (Stuttg, doi:10.1055/a-1185-8913
Bray, Rayner, Noël, Jans, Wagstaff, Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses, Antiviral Res, doi:.10.1016/j.antiviral.2020.104805
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res
Campbell, Benz, Ivermectin: a review of efficacy and safety, J Vet PharmacolTher, doi:10.1111/j.1365-2885.1984.tb00872.x
Chen, Kubo, Ivermectin and its target molecules: shared and unique modulation mechanisms of ion channels and receptors by ivermectin, J Physiol, doi:10.1113/JP275236
Guzzo, Furtek, Porras, Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects, J Clin Pharmacol, doi:10.1177/009127002401382731
Heidary, Gharebaghi, Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen, J Antibiot, doi:10.1038/s41429-020-0336-z
Jans, Wagstaff, The broad spectrum host-directed agent ivermectinas an antiviral for SARS-CoV-2?, Biochemical and Biophysical Research Communications
Meng, Jiang, Peng Xu, Chen, Qian Ni et al., A Perspective from China Zi, Radiology, doi:10.1148/radiol.2020200490
Omrani, Saad, Baig, Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study [published correction appears in, Lancet Infect Dis, doi:10.1016/S1473-3099(14)70920-X
Rajter, Sherman, Fatteh, ICON (Ivermectin in COvid Nineteen) study: Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID19, medRxiv, doi:,10.1101/2020.06.06.20124461
Schmith, Zhou, Lohmer, The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19, Clin. Pharmacol. Ther
Sharun, Dhama, Patel, Ivermectin, a new candidate therapeutic against SARS-CoV-2/COVID-19, Ann Clin Microbiol Antimicrob, doi:10.1186/s12941-020-00368-w
Yang, Atkinson, Wang, Lee, Bogoyevitch et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer, Antiviral Res, doi:.10.1016/j.antiviral.2020.104760
Ye, Wang, Mao, The pathogenesis and treatment of the `Cytokine Storm' in COVID-19, J Infect, doi:10.1016/j.jinf.2020.03.037
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Eighty-six patients with reverse ' 'transcriptase-polymerase chain reaction (RT-PCR) proven SARS-CoV-2 infection completed the ' 'trial protocol. Patients were stratified via the lottery method into two groups. Group A was ' 'administered standard of care (SOC) treatment as per existing hospital guidelines whereas ' 'group B was given ivermectin (single dose of 12 milligrams) along with SOC treatment. PCR was ' 'repeated at 72 hours, 7<jats:sup>th</jats:sup> day, and at 14<jats:sup>th</jats:sup> day of ' 'admission for both the groups and the point at which the PCR became negative was noted. ' 'Complete blood counts, liver function tests and renal function tests were done at ' 'recruitment, 7<jats:sup>th</jats:sup> day, and 14<jats:sup>th</jats:sup> day. The primary ' 'outcome was the viral clearance, measured as days to achieve PCR negativity. The secondary ' 'outcome was the development of any adverse side effects pertinent to ivermectin or ' 'derangement in baseline laboratory ' 'parameters.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In group A, ' '36 (80%) participants were males, and 9 (20%) were females, whereas in group B, 37 (90.2%) ' 'were males and 4 (9.8%) were females. Mean age was 39.0± 12.6 and 42.2 ± 12.0 years for ' 'groups A and B, respectively (p= 0.394). There was early viral clearance in group B as ' 'compared to group A (p=0.001). No adverse reaction or derangements in laboratory parameters ' 'was noted in the intervention arm during the trial ' 'period.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In the ' 'intervention arm, early viral clearance was observed and no side effects were documented. 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