Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE): Shionogi Protease Inhibitor (Ensitrelvir)

Eligibility Criteria

• * Age ≥18 years.
• * Informed consent for trial participation.
• * Hospital admission (or boarding in an emergency department or other area awaiting hospital admission) with signs and/or symptoms of a respiratory infection.
• * Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non- NAT test \[list of approved tests is in the PIM\] collected within the prior 14 days.
• * Onset of symptoms attributable to SARS-CoV2 infection occurred within 14 days before randomization.
• * Hospitalized for the management of COVID-19, with signs and/or symptoms suggestive of lower respiratory tract infection.
• * The patient is expected to be discharged from the hospital within the next 24 hours.
• * Medical condition other than the acute respiratory infection (and its manifestations) that is likely to result in death within 7 days of randomization.
• * Use of a strong CYP3A inducer within 14 days prior to enrollment
• * Moribund condition, defined as prior cardiac arrest during this hospitalization and life expectancy less than 48 hours of randomization.
• * Patient undergoing comfort care measures only such that treatment focuses on end-of- life symptom management over prolongation of life.
• * Expected inability or unwillingness to participate in study procedures.
• * In the opinion of the investigator, participation in a trial is not in the best interest of the patient.
• * Allergy to investigational agent or vehicle
• * Use of a concomitant medication that is contraindicated due to a drug-drug interaction with S-217622
• * Moderate to severe hepatic impairment (i.e., Child-Pugh class B or C) or acute liver failure.
• * Known estimated glomerular filtration rate (eGRF) \<30 mL/min/1.73m 2
• * Continuous renal replacement therapy or chronic dialysis
• * Current pregnancy
• * Current breastfeeding and unwillingness to defer breastfeeding for 30 days after the last dose of investigational agent.
• * Women of child-bearing potential who are unwilling to abstain from sexual intercourse with men or practice appropriate contraception through 30 days from the last dose of the investigational agent.
• * Men who are unwilling to abstain from sexual intercourse with women of child- bearing potential or to use barrier contraception through 30 days from the last dose of the investigational agent.
• * Inability to take investigational agent in tablet form by mouth.