AUTHOR=Rezai Mohammad Sadegh , Ahangarkani Fatemeh , Hill Andrew , Ellis Leah , Mirchandani Manya , Davoudi Alireza , Eslami Gohar , Roozbeh Fatemeh , Babamahmoodi Farhang , Rouhani Nima , Alikhani Ahmad , Najafi Narges , Ghasemian Roya , Mehravaran Hossein , Hajialibeig Azin , Navaeifar Mohammad Reza , Shahbaznejad Leila , Rahimzadeh Golnar , Saeedi Majid , Alizadeh-Navai Reza , Moosazadeh Mahmood , Saeedi Shahab , Razavi-Amoli Seyedeh-Kiana , Rezai Shaghayegh , Rostami-Maskopaee Fereshteh , Hosseinzadeh Fatemeh , Movahedi Faezeh Sadat , Markowitz John S. , Valadan Reza 

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

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.919708

DOI=10.3389/fmed.2022.919708

ISSN=2296-858X

ABSTRACT=Background: Ivermectin which was widely considered a potential treatment for COVID-19, showed uncertain clinical benefits in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug,  has been urgently needed.
Methods: 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.
Results: 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]; p-value =0.02). 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]; p-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 a p value=0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-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]; p-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]; p-value =0.16).
Conclusions: Ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission to 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 five days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19.