학술논문
Pharmacometrics of high-dose ivermectin in early COVID-19 from an open label, randomized, controlled adaptive platform trial (PLATCOV).
Document Type
Article
Author
Schilling, William H. K.; Podjanee Jittamala; Watson, James A.; Maneerat Ekkapongpisit; Tanaya Siripoon; Thundon Ngamprasertchai; Viravarn Luvira; Sasithorn Pongwilai; Cintia Cruz; Callery, James J.; Boyd, Simon; Varaporn Kruabkontho; Thatsanun Ngernseng; Jaruwan Tubprasert; Abdad, Mohammad Yazid; Nattaporn Piaraksa; Kanokon Suwannasin; Pongtorn Hanboonkunupakarn; Borimas Hanboonkunupakarn; Sakol Sookprome
Source
Subject
*IVERMECTIN
*ADAPTIVE control systems
*DRUG labeling
*SARS-CoV-2 Delta variant
*COVID-19
*COVID-19 treatment
*MONOCLONAL antibodies
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Language
ISSN
2050-084X
Abstract
Background: There is no generally accepted methodology for in vivo assessment of antiviral activity in SARS-CoV-2 infections. Ivermectin has been recommended widely as a treatment of COVID-19, but whether it has clinically significant antiviral activity in vivo is uncertain. Methods: In a multicentre open label, randomized, controlled adaptive platform trial, adult patients with early symptomatic COVID-19 were randomized to one of six treatment arms including high-dose oral ivermectin (600 µg/kg daily for 7 days), the monoclonal antibodies casirivimab and imdevimab (600 mg/600 mg), and no study drug. The primary outcome was the comparison of viral clearance rates in the modified intention-to- treat population. This was derived from daily log10 viral densities in standardized duplicate oropharyngeal swab eluates. This ongoing trial is registered at https://clinicaltrials.gov/(NCT05041907). Results: Randomization to the ivermectin arm was stopped after enrolling 205 patients into all arms, as the prespecified futility threshold was reached. Following ivermectin, the mean estimated rate of SARS-CoV- 2 viral clearance was 9.1% slower (95% confidence interval [CI] -27.2% to +11.8%; n=45) than in the no drug arm (n=41), whereas in a preliminary analysis of the casirivimab/imdevimab arm it was 52.3% faster (95% CI +7.0% to +115.1%; n=10 (Delta variant) vs. n=41). Conclusions: High-dose ivermectin did not have measurable antiviral activity in early symptomatic COVID-19. Pharmacometric evaluation of viral clearance rate from frequent serial oropharyngeal qPCR viral density estimates is a highly efficient and well-tolerated method of assessing SARS-CoV- 2 antiviral therapeutics in vitro. [ABSTRACT FROM AUTHOR]