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

Ravikirti et al., Journal of Pharmacy & Pharmaceutical Sciences, doi:10.18433/jpps32105

Ravikirti et al., Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized.., Journal of Pharmacy & Pharmaceutical Sciences, doi:10.18433/jpps32105

Jan 2021 Source PDF

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RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 patients) versus 7% (4 of 57) in the control arm. The PCR result is subject to confounding by biased loss of followup, with 23 lost in the treatment group and 13 in the control group, and 8 more people in the treatment group discharged before day 6.

This is the 11th of 46 COVID-19 RCTs for ivermectin, which collectively show efficacy with p=0.00000014.

This is the 30th of 97 COVID-19 controlled studies for ivermectin, which collectively show efficacy with p<0.0000000001 (1 in 2 sextillion).

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risk of death, 88.7% lower, RR 0.11, p = 0.12, treatment 0 of 55 (0.0%), control 4 of 57 (7.0%), NNT 14, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).

risk of mechanical ventilation, 79.3% lower, RR 0.21, p = 0.10, treatment 1 of 55 (1.8%), control 5 of 57 (8.8%), NNT 14.

risk of ICU admission, 13.6% lower, RR 0.86, p = 0.80, treatment 5 of 55 (9.1%), control 6 of 57 (10.5%), NNT 70.

risk of no hospital discharge, 88.7% lower, RR 0.11, p = 0.12, treatment 0 of 55 (0.0%), control 4 of 57 (7.0%), NNT 14, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).

risk of no viral clearance, 11.6% higher, RR 1.12, p = 0.35, treatment 42 of 55 (76.4%), control 39 of 57 (68.4%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Ravikirti et al., 9 Jan 2021, Double Blind Randomized Controlled Trial, India, peer-reviewed, 11 authors, average treatment delay 6.1 days, dosage 12mg days 1, 2.

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Evaluation of Ivermectin as a Potential Treatment for Mild to Moderate COVID-19: A Double-Blind Randomized Placebo Controlled Trial in Eastern India

Ranjini Roy, Chandrima Pattadar, Rishav Raj, Neeraj Agarwal, Dr Bijit Biswas, Pramod Kumar Manjhi, Deependra Kumar Rai, Anjani Kumar, Asim Sarfaraz, Ranjini Ravikirti, Chandrima Roy, Rishav Pattadar, Bijit Raj, Neeraj Biswas, Pramod Kumar Agarwal, Manjhi, Kumar Deependra, Rai, Anjani Shyama, Asim Kumar, Sarfaraz

There has been a growing interest in ivermectin ever since it was reported to have an in-vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This trial was conducted to test the efficacy of ivermectin in mild and moderate coronavirus disease 19 . Methods: A double blind, parallel, randomised, placebo-controlled trial conducted among adult COVID-19 patients with mild to moderate disease severity on admission in a COVID dedicated tertiary healthcare of eastern India. Enrolment was done between 1 st August and 31 st October 2020. On day 1 and 2 post enrolment, patients in the intervention arm received ivermectin 12 mg while the patients in the non-interventional arm received placebo tablets. Results: About one-fourth (23.6%) of the patients in the intervention arm and onethird (31.6%) in the placebo arm were tested reverse transcriptase polymerase chain reaction (RTPCR) negative for SARS-CoV-2 on 6 th day. Although this difference was found to be statistically insignificant [rate ratio (RR): 0.8; 95% confidence interval (CI): 0.4-1.4; p=0.348]. All patients in the ivermectin group were successfully discharged. In comparison the same for the placebo group was observed to be 93%. This difference was found to be statistically significant (RR: 1.1; 95% CI; 1.0-1.2; p=0.045). Conclusions: Inclusion of ivermectin in treatment regimen of mild to moderate COVID-19 patients could not be said with certainty based on our study results as it had shown only marginal benefit in successful discharge from the hospital with no other observed benefits.

References

Abani, Abbas, Abbas, Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial, Lancet Lond Engl, doi:10.1016/S0140-6736(21)00676-0

Agarwal, Mukherjee, Kumar, Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial), BMJ, doi:10.1136/bmj.m3939

Ahmed, Karim, Ross, A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness, Int J Infect Dis IJID Off Publ Int Soc Infect Dis, doi:10.1016/j.ijid.2020.11.191

Alam, Murshed, Bhiuyan, Saber, Alam et al., Observational Study on Clinical Features, Treatment and Outcome of COVID 19 In A Tertiary Care Centre in India-A Retrospective Case Series, J Bangladesh Coll Physicians Surg, doi:10.3329/jbcps.v38i0.47512

Ashour, Ivermectin: From theory to clinical application, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2019.05.003

Babalola, Bode, Ajayi, Ivermectin shows clinical benefits in mild to moderate COVID19: a randomized controlled double-blind, dose-response study in Lagos, QJM Int J Med. Published online, doi:10.1093/qjmed/hcab035

Beigel, Tomashek, Dodd, Remdesivir for the Treatment of Covid-19 -Final Report, N Engl J Med, doi:10.1056/NEJMoa2007764

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

Cao, Wang, Wen, A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19, N Engl J Med, doi:10.1056/NEJMoa2001282

Chaccour, Casellas, Blanco-Di Matteo, The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with nonsevere COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial, EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720

Gonzalez, Gonzalez, Ueno, Ivermectin in Human Medicine, An Overview of the Current Status of Its Clinical Applications, Curr Pharm Biotechnol, doi:10.2174/138920112800399248

Heidary, Gharebaghi, Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen, J Antibiot, doi:10.1038/s41429-020-0336-z

Horby, Lim, Emberson, Dexamethasone in Hospitalized Patients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2021436

Insiat, Rabby, Current Drugs with Potential for Treatment of COVID-19: A Literature Review, J Pharm Pharm Sci, doi:10.18433/jpps31002

Khan, Khan, Debnath, Ivermectin Treatment May Improve the Prognosis of Patients With COVID-19, Arch Bronconeumol, doi:10.1016/j.arbres.2020.08.007

Kinobe, Owens, A systematic review of experimental evidence for antiviral effects of ivermectin and an in silico analysis of ivermectin's possible mode of action against SARS-CoV-2, Fundam Clin Pharmacol, doi:10.1111/fcp.12644

López-Medina, López, Hurtado, Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial, JAMA, doi:10.1001/jama.2021.3071

Mahmud, Rahman, Alam, Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial, J Int Med Res, doi:10.1177/03000605211013550

Okumuş, Demirtürk, Çetinkaya, Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients, BMC Infect Dis, doi:10.1186/s12879-021-06104-9

Padhy, Mohanty, Das, Meher, Therapeutic potential of ivermectin as add on treatment in COVID 19: A systematic review and meta-analysis, J Pharm Pharm Sci, doi:10.18433/jpps31457

Rajter, Sherman, Fatteh, Vogel, Sacks et al., Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study, Chest, doi:10.1016/j.chest.2020.10.009

Shahbaznejad, Davoudi, Eslami, Effect of ivermectin on COVID-19: A multicenter double-blind randomized controlled clinical trial, Clin Ther. Published online, doi:10.1016/j.clinthera.2021.04.007

Sterne, Murthy, Diaz, Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis, JAMA, doi:10.1001/jama.2020.17023

Surkova, Nikolayevskyy, Drobniewski, False-positive COVID-19 results: hidden problems and costs, Lancet Respir Med, doi:10.1016/S2213-2600(20)30453-7

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