Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV)
Podjanee Jittamala, William HK 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 Santana Aguiar, Franciele Martins Santos, Elizabeth M. Batty, Pongtorn Hanboonkunupakarn, Borimas Hanboonkunupakarn, Sakol Sookprome, Kittiyod Poovorawan, Mallika Imwong, Walter Taylor, Vasin Chotivanich, Chunlanee Sangketchon, Wiroj Ruksakul, Kesinee Chotivanich, Sasithon Pukrittayakamee, Arjen M. Dondorp, Nicholas Day, Mauro Martins Teixeira, Watcharapong Piyaphanee, Weerapong Phumratanaprapin, Nicholas J. White, for the PLATCOV Collaborative Group, Nicholas J. White, William HK Schilling, Viravarn Luvira, James J. Callery, Nicholas P. J. Day, Sasithon Pukrittayakamee, Simon Boyd, Cintia Cruz, Arjen M. Dondorp, Walter Taylor, James A Watson, Watcharapong Piyaphanee, Kittiyod Poovorawan, Thundon Ngamprasertchai, Tanaya Siripoon, Borimas Hanboonkunupakarn, Kesinee Chotivanich, Podjanee Jittamala, Mallika Imwong, Maneerat Ekkapongpisit, Varaporn Kruabkontho, Thatsanun Ngernseng, Jaruwan Tubprasert, Mohammad Yazid Abdad, Srisuda Keayarsa, Orawan Anunsittichai, Maliwan Hongsuwan, Yutatirat Singhaboot, Wanassanan Madmanee, Elizabeth M. Batty, Runch Tuntipaiboontana, Watcharee Pagornrat, Vasin Chotivanich, Wiroj Ruksakul, Chunlanee Sangketchon, Pongtorn Hanboonkunupakarn, Sakol Sookprome, Mauro Martins Teixeira, Pedro J Almeida, Renato Santana Aguiar, Franciele Martins Santos
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 log10 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.