Covid-19 Living Data

Trial jRCT2031210350
Publication Mukae H, medRxiv (2022) (preprint)
Dates: 2022-01-02 to 2022-02-09
Funding: Mixed (Shionogi & Co., Ltd. ; Organization of the Ministry of Health, Labour and Welfare. Employees of Shionogi & Co., Ltd., participated in and approved the design and conduct of the study; wrote the protocol; and were involved in the collection, management, analysis, and interpretation of data. Institutional authors reviewed and approved the protocol and collected and interpreted the data.)
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / Japan, South Korea Follow-up duration (days): 28
Inclusion criteria	Patients aged 12 to 69 years tested positive for SARS-CoV-2 (assessed by SARS-CoV-2 antigen or nucleic acid detection testing) within 120 hours prior to randomization patients aged <20 years should have recorded a body weight of ≥40 kg at enrollment at least one moderate or severe symptom or worsening of an existing symptom among the 12 COVID-19 symptoms (stuffy or runny nose, sore throat, shortness of breath, cough, low energy or tiredness, muscle or body aches, headache, chills or shivering, feeling hot or feverish, nausea, vomiting, or diarrhea) and a symptom duration of ≤120 hours patients were eligible for enrollment irrespective of treatment settings (inpatient, outpatient, recuperation at home, or recuperation at designated hotels) because some of them required hospitalization or recuperation for the purpose of isolation or clinical trial participation, regardless of disease severity, at the time of this research.
Exclusion criteria	Awake oxygen saturation of ≤93% (room air) oxygen administration likely worsening of COVID-19 within 48 hours from randomization in the opinion of the investigator suspected active and systemic infections requiring treatment (except for COVID-19) current or chronic history of moderate or severe liver disease, known hepatic or biliary abnormalities (except for Gilbert’s syndrome or asymptomatic gallstones), or moderate-to-severe kidney disease pregnant, possibly pregnant, or breastfeeding women and blood donation (≥400 mL within 12 weeks or ≥200 mL within 4 weeks prior to enrollment) used drugs for SARS-CoV-2 infection within 7 days prior to randomization or a strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitor or inducer or St. John’s wort products within 14 days prior to randomization.
Interventions
	Treatment Ensitrelvir 250 Initial dose: 750 mg orally once daily on day 1 - Maintenance dose: 250 mg orally once daily on days 2-5 Ensitrelvir 125 Initial dose: 375 mg orally once daily on day 1 - Maintenance dose: 125 mg orally once daily on days 2-5
	Control Placebo
Participants
	Randomized participants : Placebo=143 Ensitrelvir 250=143 Ensitrelvir 125=142
	Characteristics of participants N= 428 Mean age : NR 199 males Severity : Mild: n= 428/ Asymptomatic: n=0 Number of vaccinated participants: 194
Primary outcome
	In the register Change in total score of 12 symptoms of COVID-19 from Day 1 to Day 6 per unit time ; Day 4 Change in virus titer of SARS-CoV-2 from baseline.
	In the report Change from baseline (day 1, before drug administration) in the SARS-CoV-2 viral titer on day 4 of treatment ; change from baseline up to 120 hours in the total score of COVID-19 symptoms.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the prospective trial registry and supplementary appendices were used in data extraction and assessment of risk of bias. There is no change from the trial registration in the intervention and control treatments. The primary outcomes in the article reflect those in the registry. The trial (n = 428) did not achieve its target sample size (n = 435). This paper reports on a part b of a 2 part phase 2 trial. The study was updated on November 18th, 2022 with data extracted after contact with authors.