Author:
Schilling William HK,Jittamala Podjanee,Watson James A,Ekkapongpisit Maneerat,Siripoon Tanaya,Ngamprasertchai Thundon,Luvira Viravarn,Pongwilai Sasithon,Cruz Cintia,Callery James J,Boyd Simon,Kruabkontho Varaporn,Ngernseng Thatsanun,Tubprasert Jaruwan,Abdad Mohammad Yazid,Piaraksa Nattaporn,Suwannasin Kanokon,Hanboonkunupakarn Pongtorn,Hanboonkunupakarn Borimas,Sookprome Sakol,Poovorawan Kittiyod,Thaipadungpanit Janjira,Blacksell Stuart,Imwong Mallika,Tarning Joel,Taylor Walter RJ,Chotivanich Vasin,Sangketchon Chunlanee,Ruksakul Wiroj,Chotivanich Kesinee,Teixeira Mauro M,Pukrittayakamee Sasithon,Dondorp Arjen M,Day Nicholas PJ,Piyaphanee Watcharapong,Phumratanaprapin Weerapong,White Nicholas J
Abstract
ABSTRACTBackgroundThere is no generally accepted methodology for in vivo assessment of antiviral activity in SARS-CoV-2 infection. Ivermectin has been recommended widely as a treatment of COVID-19, but whether it has significant antiviral activity in vivo is uncertain.MethodsIn 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 ivermectin (600µg/kg daily for seven days), the monoclonal antibodies casirivimab and imdevimab (600mg/600mg), and no study drug. Viral clearance rates were derived from daily duplicate oropharyngeal quantitative PCR measurements. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907).ResultsRandomization to the ivermectin arm was stopped after enrolling 205 patients into all arms, as the prespecified futility threshold was reached. Compared with the no study drug arm, the mean estimated SARS-CoV-2 viral clearance following ivermectin was 9.1% slower [95%CI -27.2% to +11.8%; n=45 versus 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) versus n=41].ConclusionsHigh dose ivermectin did not have measurable antiviral activity in early symptomatic COVID-19. Measured in this way viral clearance rate is a valuable pharmacodynamic measure in assessing antiviral COVID-19 therapeutics in vivo.Funding“Finding treatments for COVID-19: A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in early symptomatic COVID-19 (PLAT-COV)” is funded by the Wellcome Therapeutics Accelerator (223195/Z/21/Z).ImpactRate of viral clearance determined from daily duplicate oropharyngeal swabs over one week is an efficient measure of antiviral efficacy in early COVID-19 infection.High dose ivermectin did not demonstrate measurable antiviral activity in early symptomatic COVID-19 infection.
Publisher
Cold Spring Harbor Laboratory