Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials

DOI record: { "DOI": "10.3389/fmed.2022.919708", "ISSN": [ "2296-858X" ], "URL": "http://dx.doi.org/10.3389/fmed.2022.919708", "abstract": "<jats:sec><jats:title>Background</jats:title><jats:p>Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04–1.66]; <jats:italic>p</jats:italic>-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15–1.45]; <jats:italic>p</jats:italic>-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with <jats:italic>p</jats:italic> value = 0.020. On the day seventh of treatment, fever (<jats:italic>p</jats:italic>-value = 0.040), cough (<jats:italic>p</jats:italic>-value = 0.019), and weakness (<jats:italic>p</jats:italic>-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65–2.84]; <jats:italic>p</jats:italic>-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60–1.09]; <jats:italic>p</jats:italic>-value = 0.16).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Clinical Trial Registration</jats:title><jats:p><jats:ext-link>www.irct.ir</jats:ext-link> IRCT20111224008507N5 and IRCT20111224008507N4.</jats:p></jats:sec>", "alternative-id": [ "10.3389/fmed.2022.919708" ], "author": [ { "affiliation": [], "family": "Rezai", "given": "Mohammad Sadegh", "sequence": "first" }, { "affiliation": [], "family": "Ahangarkani", "given": "Fatemeh", "sequence": "additional" }, { "affiliation": [], "family": "Hill", "given": "Andrew", "sequence": "additional" }, { "affiliation": [], "family": "Ellis", "given": "Leah", "sequence": "additional" }, { "affiliation": [], "family": "Mirchandani", "given": "Manya", "sequence": "additional" }, { "affiliation": [], "family": "Davoudi", "given": "Alireza", "sequence": "additional" }, { "affiliation": [], "family": "Eslami", "given": "Gohar", "sequence": "additional" }, { "affiliation": [], "family": "Roozbeh", "given": "Fatemeh", "sequence": "additional" }, { "affiliation": [], "family": "Babamahmoodi", "given": "Farhang", "sequence": "additional" }, { "affiliation": [], "family": "Rouhani", "given": "Nima", "sequence": "additional" }, { "affiliation": [], "family": "Alikhani", "given": "Ahmad", "sequence": "additional" }, { "affiliation": [], "family": "Najafi", "given": "Narges", "sequence": "additional" }, { "affiliation": [], "family": "Ghasemian", "given": "Roya", "sequence": "additional" }, { "affiliation": [], "family": "Mehravaran", "given": "Hossein", "sequence": "additional" }, { "affiliation": [], "family": "Hajialibeig", "given": "Azin", "sequence": "additional" }, { "affiliation": [], "family": "Navaeifar", "given": "Mohammad Reza", "sequence": "additional" }, { "affiliation": [], "family": "Shahbaznejad", "given": "Leila", "sequence": "additional" }, { "affiliation": [], "family": "Rahimzadeh", "given": "Golnar", "sequence": "additional" }, { "affiliation": [], "family": "Saeedi", "given": "Majid", "sequence": "additional" }, { "affiliation": [], "family": "Alizadeh-Navai", "given": "Reza", "sequence": "additional" }, { "affiliation": [], "family": "Moosazadeh", "given": "Mahmood", "sequence": "additional" }, { "affiliation": [], "family": "Saeedi", "given": "Shahab", "sequence": "additional" }, { "affiliation": [], "family": "Razavi-Amoli", "given": "Seyedeh-Kiana", "sequence": "additional" }, { "affiliation": [], "family": "Rezai", "given": "Shaghayegh", "sequence": "additional" }, { "affiliation": [], "family": "Rostami-Maskopaee", "given": "Fereshteh", "sequence": "additional" }, { "affiliation": [], "family": "Hosseinzadeh", "given": "Fatemeh", "sequence": "additional" }, { "affiliation": [], "family": "Movahedi", "given": "Faezeh Sadat", "sequence": "additional" }, { "affiliation": [], "family": "Markowitz", "given": "John S.", "sequence": "additional" }, { "affiliation": [], "family": "Valadan", "given": "Reza", "sequence": "additional" } ], "container-title": "Frontiers in Medicine", "container-title-short": "Front. 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