The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial
Carlos Chaccour, Aina Casellas, Andrés Blanco-Di Matteo, Iñigo Pineda, Alejandro Fernandez-Montero, Paula Ruiz-Castillo, Mary-Ann Richardson, Mariano Rodríguez-Mateos, Carlota Jordán-Iborra, Joe Brew, Francisco Carmona-Torre, Miriam Giráldez, Ester Laso, Juan C Gabaldón-Figueira, Carlota Dobaño, Gemma Moncunill, José R Yuste, Jose L Del Pozo, N Regina Rabinovich, Verena Schöning, Felix Hammann, Gabriel Reina, Belen Sadaba, Mirian Fernández-Alonso
EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720
Background: Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods: Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings: All patients recruited completed the trial (median age, 26 [IQR 19À36 in the ivermectin and 21À44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0¢92, 95% CI: 0¢77À1¢09, p = 1¢0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0¢24 for gene E; p = 0¢18 for gene N) and day 7 (p = 0¢16 for gene E; p = 0¢18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0¢24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation: Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the
treatment in the ivermectin group with differences increasing from 3-fold lower at day 4 (p = 0¢24 for gene E; p = 0¢18 for gene N) to around 18-fold lower at day 7 (p = 0¢16 for gene E; p = 0¢18 for gene N) (Fig. 2 and Table S1 ). A similar tendency remained for the viral load at days 14 and 21, with values from patients in the ivermectin group consistently lower for at least one of the genes, the difference was not statistically significant at any single point (Fig. 2 and Table S1 ). The values of cycle thresholds had a very similar behavior (Figure S1 ). Summary statistics for viral kinetics are provided in Table S2 . a Hours before dosing b The slightly higher median systolic blood pressure in the placebo group at baseline was not seen in subsequent study visits and was judged as non-clinically significant, see table S3 for the evolution of all vital signs throughout the study, *Reported or measured fever. IQR: interquartile range
Author contributions Carlos Chaccour and Aina Casellas had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualization
Supplementary materials Supplementary material associated with this article can be found in the online version at doi:10.1016/j.eclinm.2020.100720.
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