Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV)
Jittamala P., Schilling WHK., Watson JA., Luvira V., Siripoon T., Ngamprasertchai T., Almeida PJ., Ekkapongpisit M., Cruz C., Callery JJ., Boyd S., Anunsittichai O., Hongsuwan M., Singhaboot Y., Pagornrat W., Tuntipaiboontana R., Kruabkontho V., Ngernseng T., Tubprasert J., Abdad MY., Keayarsa S., Madmanee W., Aguiar RS., Santos FM., Batty EM., Hanboonkunupakarn P., Hanboonkunupakarn B., Sookprome S., Poovorawan K., Imwong M., Taylor WRJ., Chotivanich V., Sangketchon C., Ruksakul W., Chotivanich K., Pukrittayakamee S., Dondorp AM., Day NPJ., Teixeira MM., Piyaphanee W., Phumratanaprapin W., White NJ., White NJ., Schilling WHK., Luvira V., Callery JJ., Day NPJ., Pukrittayakamee S., Boyd S., Cruz C., Dondorp AM., Taylor WRJ., Watson JA., Piyaphanee W., Poovorawan K., Ngamprasertchai T., Siripoon T., Hanboonkunupakarn B., Chotivanich K., Jittamala P., Imwong M., Ekkapongpisit M., Kruabkontho V., Ngernseng T., Tubprasert J., Abdad MY., Keayarsa S., Anunsittichai O., Hongsuwan M., Singhaboot Y., Madmanee W., Batty EM., Tuntipaiboontana R., Pagornrat W., Chotivanich V., Ruksakul W., Sangketchon C., Hanboonkunupakarn P., Sookprome S., Teixeira MM., Almeida PJ., Aguiar RS., Santos FM.
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.