UMIN-ICDS Clinical Trial

Public title

A study on the association between early antiviral treatment and hospitalization within 30 days in high-risk outpatients with mild COVID-19

Acronym

COVID Antiviral-Hospitalization Study

Scientific Title

Early antiviral treatment with Paxlovid, Molnupiravir, or Ensitrelvir and 30-day hospitalization in high-risk outpatients with COVID-19: a target trial emulation study

Scientific Title:Acronym

COVID-19 Antiviral TTE Study

Region

Japan

Condition

COVID-19

Classification by specialty

Infectious disease

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the association between early antiviral treatment (nirmatrelvir/ritonavir, molnupiravir, or ensitrelvir) and 30-day all-cause hospitalization among high-risk outpatients with COVID-19 using a target trial emulation framework.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

The primary outcome was 30-day all-cause hospitalization, defined as any inpatient or Diagnosis Procedure Combination (DPC) claim with an admission date between day 1 and day 30 after the index date.

Key secondary outcomes

Secondary outcomes were 30-day COVID-19-related hospitalization and 30-days severe COVID-19-related hospitalization. Severe hospitalization defined as hospitalization requiring supplemental oxygen, non invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Adults (aged 18 years or older) with an outpatient diagnosis of COVID-19 who were at high risk of progression to severe disease and did not require hospitalization at diagnosis were eligible. High-risk patients were defined as those aged 65 years or older or those aged 18-64 years with at least one prespecified risk factor for severe disease. Eligible episodes were identified between 1 July 2023 and 31 May 2025, and the qualifying diagnosis date was defined as the index date.

Key exclusion criteria

Episodes were excluded if they met any of the following criteria: simultaneous prescription of multiple target antivirals, in-hospital oral antiviral administration, outpatient remdesivir treatment, or missing essential variables (sex, date of birth, or observation start).

Target sample size

1000000

Name of lead principal investigator

1st name	Satoshi
Middle name
Last name	Kutsuna

Organization

The University of Osaka, Graduate School of Medicine Faculty of Medicine

Division name

Department of Infection Prevention and Control

Zip code

565-0871

Address

2-2, Yamadaoka, Suita city

TEL

0836-6879-5111

Email

kutsuna@hp-infect.osaka-u.ac.jp

Name of contact person

1st name	Satoshi
Middle name
Last name	Kutsuna

Organization

The University of Osaka, Graduate School of Medicine Faculty of Medicine

Division name

Department of Infection Prevention and Control

Zip code

565-0871

Address

2-2, Yamadaoka, Suita city

TEL

0836-6879-5111

Homepage URL

Email

kutsuna@hp-infect.osaka-u.ac.jp

Institute

The University of Osaka

Institute

Department

Personal name

Organization

The University of Osaka

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

The University of Osaka Hospital, Ethical Review Board

Address

2-15, Yamadaoka, Suita city

Tel

0836-6879-5111

Email

rinri@hp-crc.med.osaka-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

大阪大学大学院医学系研究科 感染制御学/ The University of Osaka, Graduate School of Medicine

Date of disclosure of the study information

2026

Year

07

Month

03

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2026

Year

06

Month

10

Day

Date of IRB

Anticipated trial start date

2026

Year

07

Month

04

Day

Last follow-up date

2026

Year

07

Month

04

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This study is a retrospective cohort study using anonymized JMDC Claims Database and JMDC Late-Stage Elderly Healthcare Database data and is designed according to the Target Trial Emulation framework. The study includes high-risk outpatients with newly diagnosed COVID-19 and compares four treatment strategies: three oral antiviral agents (nirmatrelvir/ritonavir [Paxlovid], molnupiravir, and ensitrelvir) and no antiviral treatment. The primary outcome is 30-day all-cause hospitalization, while secondary outcomes include 30-day COVID-19-related hospitalization and severe COVID-19-related hospitalization.

Registered date

2026

Year

07

Month

02

Day

Last modified on

2026

Year

07

Month

02

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000071086