Prospective Study of Treatment with Ensitrelvir for COVID-19 in Patients Undergoing Hemodialysis (PROTECT-HD)

INTRODUCTION: Patients on hemodialysis (HD) are vulnerable to COVID-19 and often excluded from pivotal antiviral trials. Ensitrelvir, an oral SARS-CoV-2 3C-like protease inhibitor approved in Japan, remains unevaluated in patients undergoing HD. This study assesses the pharmacokinetics, antiviral activity, safety, and clinical effectiveness of ensitrelvir in participants with mild COVID-19 undergoing HD. METHODS: In this prospective, single-arm, open-label study (December 2024-April 2025), participants with mild COVID-19 undergoing HD received ensitrelvir 375 mg on Day 1, followed by 125 mg once daily on Days 2-5. On Visit 2 (Day 3), plasma ensitrelvir concentrations were measured at three time points prior to ensitrelvir administration-before, during, and after dialysis. On Visit 3 (Day 5), blood samples were collected after dialysis and prior to ensitrelvir administration. Clinical outcomes, body temperature, SARS-CoV-2 viral load, and viral titers were monitored through Day 8. The primary endpoint was plasma concentration of ensitrelvir relative to dialysis; secondary endpoints included clinical outcomes, body temperature, and changes in viral load. RESULTS: copies/mL from baseline to Day 8. No treatment-emergent adverse events, hospitalizations, or severe COVID-19-related complications occurred. CONCLUSION: No dose adjustment was required regardless of HD. In participants with mild COVID-19 undergoing HD, plasma ensitrelvir concentrations were similar to those previously reported in healthy individuals. Ensitrelvir showed favorable antiviral and clinical responses, supporting its safe use without dose adjustments. TRIAL REGISTRATION: Japan Registry of Clinical Trials ID: jRCTs071240069.