High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial
MD Dora Buonfrate, MD Fabio Chesini, MD Davide Martini, MSc Maria Carla Roncaglioni, MSc Maria Luisa Ojeda Fernandez, MSc Maria Francesca Alvisi, MSc Irene De Simone, PhD Eliana Rulli, PhD Alessandro Nobili, MD Giacomo Casalini, Prof Spinello Antinori, PharmD Marco Gobbi, MD Caterina Campoli, PhD Michela Deiana, PhD Elena Pomari, PharmD Gianluigi Lunardi, PharmD Roberto Tessari, PhD Zeno Bisoffi
International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2021.106516
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47 years (Q1[first quartile]-Q3[third quartile] 31.0-58.0). The majority were Europeans (97%). Comorbidities were reported by one third of the participants. Eighty (86%) participants were symptomatic with a median duration of 4 days, cough being the most frequent symptom, followed by fever and fatigue. The severity score was 1 for 78 participants (84%), and 2 for 15 (16%). Details of main physical findings, baseline laboratory exams and concomitant treatments are summarized in Supplementary Tables 3, 4 and 5. Summary of treatment compliance is reported in Table 2 . Fourteen participants (4.3%) discontinued the treatment: 1 (3.1%) in arm A, 2 (6.9%) in arm B and 11 (34.4%) in arm C. The interruptions in arm C were all due to tolerability. Seven participants received only one day of treatment, three received two and three days, respectively, and one received four days (Supplementary Table 6 ). No SADRs were observed in any of the study groups. Results on the viral load (Log10) at day 7 versus baseline, are summarized in Table 3 . In arm C, the mean reduction of the viral load was 2.9 (SD 1.6), versus 2.5 (2.2) in arm B and 2.0 (2.1) in arm A. The observed effect size (versus arm A) was 0.48 for arm C and 0.21 for arm B. Differences were not normally distributed (Shapiro-Wilk test p value <0.0001 for both comparisons), thus Wilcoxon exact test was also performed. The differences were not significant (p=0.099 and 0.122 for C versus A and B versus A, respectively). Results..
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