Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV)
Authors: Jittamala Podjanee , Schilling William H K , Watson James A , Luvira Viravarn , Siripoon Tanaya , Ngamprasertchai Thundon , Almeida Pedro J , Ekkapongpisit Maneerat , Cruz Cintia , Callery James J , Boyd Simon , Anunsittichai Orawan , Hongsuwan Maliwan , Singhaboot Yutatirat , Pagornrat Watcharee , Tuntipaiboontana Runch , Kruabkontho Varaporn , Ngernseng Thatsanun , Tubprasert Jaruwan , Abdad Mohammad Yazid , Keayarsa Srisuda , Madmanee Wanassanan , Aguiar Renato S , Santos Franciele M , Batty Elizabeth M , Hanboonkunupakarn Pongtorn , Hanboonkunupakarn Borimas , Sookprome Sakol , Poovorawan Kittiyod , Imwong Mallika , Taylor Walter R J , Chotivanich Vasin , Sangketchon Chunlanee , Ruksakul Wiroj , Chotivanich Kesinee , Pukrittayakamee Sasithon , Dondorp Arjen M , Day Nicholas P J , Teixeira Mauro M , Piyaphanee Watcharapong , Phumratanaprapin Weerapong , White Nicholas J ,   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 
Published: July 2023

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.