A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
Sabeena Ahmed, Mohammad Mahbubul Karim, Allen G Ross, Mohammad Sharif Hossain, John D Clemens, Mariya Kibtiya Sumiya, Ching Swe Phru, Mustafizur Rahman, Khalequ Zaman, Jyoti Somani, Rubina Yasmin, Mohammad Abul Hasnat, Ahmedul Kabir, Asma Binte Aziz, Wasif Ali Khan
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.191
Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.
Ethical review The trial was approved by the Institutional Review Board (Research Review Committee and Ethical Review Committee) of icddr,b and subsequently by the National Ethics Review Committee of Bangladesh Medical Research Council and Clinical Trial Advisory Committee of the Directorate General of Drug Administration, Government of Bangladesh. Written informed consent was obtained from all patients.
Declaration of interests The authors declare that there are no known competing financial interests or personal relationships that could have appeared to influence the work described in this paper.
Conflicts of interest The authors have no conflicts of interest to declare.
Author agreement All authors have seen and approved the final version of the manuscript being submitted. The article is the authors' original work, has not received prior publication, and is not under consideration for publication elsewhere.
References
Alam, Murshed, Bhiuyan, Saber, Alam, A Case Series of 100 COVID-19 Positive Patients Treated with Combination of Ivermectin and Doxycycline, J Bangladesh Coll Physic Surg,
doi:10.3329/jbcps.v38i0.47512Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro Antiviral Res
Chiu, Lu, Metabolism and tissue residues
Lespine, Alvinerie, Sutra, Pors, Chartier, Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat, Vet Parasitol
Rajter, Sherman, Fatteh, Vogel, Sacks et al., ICON (Ivermectin in COvid Nineteen) study: use of ivermectin is associated with lower mortality in hospitalised patients with COVID-19, medRxiv
Wu, Liu, Yang, Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharm Sin B,
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