Abstract Background Uncertainty over the therapeutic benefit of parenteral remdesivir in coronavirus disease 2019 (COVID-19) has resulted in varying treatment guidelines. Methods In a multicenter open-label, controlled, adaptive, pharmacometric platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to 1 of 8 treatment arms including intravenous remdesivir (200 mg followed by 100 mg daily for 5 days) or no study drug. The primary outcome was the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance (estimated under a linear model fit to the daily log 10 viral densities, days 0–7) in standardized duplicate oropharyngeal swab eluates, in a modified intention-to-treat population. This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907). Results The 2 study arms enrolled 131 patients (remdesivir n = 67, no study drug n = 64) and estimated viral clearance rates from a median of 18 swab samples per patient (a total of 2356 quantitative polymerase chain reactions). Under the linear model, compared with the contemporaneous control arm (no study drug), remdesivir accelerated mean estimated viral clearance by 42% (95% credible interval, 18%–73%). Conclusions Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Pharmacometric assessment of therapeutics using the method described can determine in vivo clinical antiviral efficacy rapidly and efficiently. In early symptomatic COVID-19, intravenous remdesivir accelerated viral clearance compared with no treatment.
Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV)
[저자] Podjanee Jittamala, William H K Schilling, James A Watson, Viravarn Luvira, Tanaya Siripoon, Thundon Ngamprasertchai, Pedro J Almeida, Maneerat Ekkapongpisit, Cintia Cruz, James J Callery, Simon Boyd, Orawan Anunsittichai, Maliwan Hongsuwan, Yutatirat Singhaboot, Watcharee Pagornrat, Runch Tuntipaiboontana, Varaporn Kruabkontho, Thatsanun Ngernseng, Jaruwan Tubprasert, Mohammad Yazid Abdad, Srisuda Keayarsa, Wanassanan Madmanee, Renato S Aguiar, Franciele M Santos, Elizabeth M Batty, Pongtorn Hanboonkunupakarn, Borimas Hanboonkunupakarn, Sakol Sookprome, Kittiyod Poovorawan, Mallika Imwong, Walter R J Taylor, Vasin Chotivanich, Chunlanee Sangketchon, Wiroj Ruksakul, Kesinee Chotivanich, Sasithon Pukrittayakamee, Arjen M Dondorp, Nicholas P J Day, Mauro M Teixeira, Watcharapong Piyaphanee, Weerapong Phumratanaprapin, Nicholas J White, for the PLATCOV Collaborative Group
White Nicholas J Schilling William H K Luvira Viravarn Callery James J Day Nicholas P J Pukrittayakamee Sasithon Boyd Simon Cruz Cintia Dondorp Arjen M Taylor Walter R J Watson James A Piyaphanee Watcharapong Poovorawan Kittiyod Ngamprasertchai Thundon Siripoon Tanaya Hanboonkunupakarn Borimas Chotivanich Kesinee Jittamala Podjanee Imwong Mallika Ekkapongpisit Maneerat Kruabkontho Varaporn Ngernseng Thatsanun Tubprasert Jaruwan Abdad Mohammad Yazid Keayarsa Srisuda Anunsittichai Orawan Hongsuwan Maliwan Singhaboot Yutatirat Madmanee Wanassanan Batty Elizabeth M Tuntipaiboontana Runch Pagornrat Watcharee Chotivanich Vasin Ruksakul Wiroj Sangketchon Chunlanee Hanboonkunupakarn Pongtorn Sookprome Sakol Teixeira Mauro M Almeida Pedro J Aguiar Renato S Santos Franciele M
[Category] update2024,
[Article Type] article
[Source] pmc
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