Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV)
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, Nicholas J White, William Hk Schilling, Viravarn Luvira, James J Callery, Nicholas Pj Day, Sasithon Pukrittayakamee, Simon Boyd, Cintia Cruz, Arjen M Dondorp, Walter Rj 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 M Teixeira, Pedro J Almeida, Renato S Aguiar, Franciele M Santos
The Journal of Infectious Diseases, doi:10.1093/infdis/jiad275
Background: Uncertainty over the therapeutic benefit provided by parenteral remdesivir in COVID-19 has resulted in varying treatment guidelines.
Methods: In a multicenter open label, controlled, adaptive, pharmacometric platform trial, lowrisk adult patients with early symptomatic COVID-19 were randomized to one of eight treatment arms including intravenous remdesivir (200mg followed by 100mg daily for five days) or no study drug. The primary outcome was the rate of viral 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 (mITT). This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907).
Results: The two 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 qPCRs). Under the linear model, compared with the contemporaneous control arm (no study drug), remdesivir accelerated mean estimated SARS-CoV-2 viral clearance by 42% (95% credible interval [CI] 18 to 73). Interpretation: Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Pharmacometric assessment of therapeutics using the described method can rapidly and efficiently determine in vivo clinical efficacy.
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