UMIN-ICDS Clinical Trial
| Unique ID issued by UMIN | UMIN000062764 |
|---|---|
| Receipt number | R000071861 |
| Scientific Title | Early oral antiviral therapy and subacute post-COVID symptom burden: a target trial emulation using the JMDC claims database |
| Date of disclosure of the study information | 2026/09/01 |
| Last modified on | 2026/09/01 14:26:01 |
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Basic information
Public title
A study of whether initiating an oral SARS-CoV-2 antiviral (ensitrelvir, nirmatrelvir/ritonavir, or molnupiravir) on the day of outpatient COVID-19 diagnosis reduces newly recorded subacute post-COVID symptoms (impaired smell, impaired taste, fatigue, cough, appetite loss) during days 29-60 after diagnosis, using a Japanese claims database (target trial emulation)
Acronym
Early Antiviral and Subacute Post-COVID Symptoms TTE Study (JMDC)
Scientific Title
Early oral antiviral therapy and subacute post-COVID symptom burden: a target trial emulation using the JMDC claims database
Scientific Title:Acronym
Antiviral Subacute Post-COVID Symptom TTE Study (JMDC)
Region
| Japan |
Condition
Condition
COVID-19 (acute COVID-19 diagnosed in outpatient care). The outcome is subacute post-COVID symptoms (impaired smell, impaired taste, fatigue, cough, appetite loss).
Classification by specialty
| Medicine in general | Infectious disease | Oto-rhino-laryngology |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
Using the JMDC insurer claims database, to estimate whether initiating an oral SARS-CoV-2 antiviral (ensitrelvir, nirmatrelvir/ritonavir, or molnupiravir) on the day of outpatient COVID-19 diagnosis (day 0), compared with not initiating, reduces the risk of newly recorded subacute post-COVID symptoms (impaired smell/taste, fatigue, cough, appetite loss) during days 29-60 after diagnosis (the claim month following the index month, m1), within a day-0 new-user target trial emulation framework. Propensity-score overlap weighting and inverse-probability-of-censoring weighting (IPCW) are used. This registration is performed before viewing any treatment effect.
Basic objectives2
Efficacy
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Pragmatic
Developmental phase
Not applicable
Assessment
Primary outcomes
The primary outcome is a newly recorded diagnosis in any of five symptom domains during the claim month following the index month (m1, approximately days 29-60): impaired smell (R43.0, R43.1), impaired taste (R43.2, R43.8, R43.9), fatigue (R53), cough (R05), and appetite loss (R63.0). Newly recorded requires no record of the same domain in the preceding six claim months; the event date is set to the 15th of m1. Day-60 risks, risk ratio, and risk difference are estimated using a weighted Aalen-Johansen estimator (death as a competing event) after propensity-score overlap weighting and IPCW, with 95% CIs from 2,000 bootstrap replicates resampling index diagnosing facilities. This outcome is designated subacute post-COVID symptom burden and does not meet the WHO three-month criterion for post COVID-19 condition.
Key secondary outcomes
Secondary: (1) a high-specificity composite (impaired smell, impaired taste, post-viral fatigue syndrome, alopecia) in m1; (2) domain-specific analyses with a global test of directional consistency; (3) a difference-in-differences using each patient own pre-infection background rate; (4) the composite over m1-m3; (5) the composite over m2-m3 (prespecified as a demonstration of non-measurability); (6) the count of affected symptom domains; and (7) drug-specific comparisons (ensitrelvir; nirmatrelvir/ritonavir; molnupiravir), Holm-adjusted with familywise 95% simultaneous confidence intervals. Sensitivity analyses include a quantitative bias analysis, negative-control outcomes (fracture, appendicitis, urolithiasis), and healthcare-contact diagnostics.
Base
Study type
Observational
Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
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
Eligibility
Age-lower limit
| 18 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
(1) Age 18 years or older at index. (2) The first eligible outpatient episode with a confirmed acute COVID-19 diagnosis (standard disease codes 8850104 / 8850701; suspected-flag records excluded) between 1 April 2024 and 31 March 2025. (3) Continuous enrollment from day -365 through day 0. (4) Not hospitalised on day 0. (5) No acute COVID-19 diagnosis in the prior 180 days. (6) A non-empty drug-specific eligibility set (no claims-identifiable contraindication or contraindicated co-medication for at least one of the three oral antivirals: ensitrelvir, nirmatrelvir/ritonavir, molnupiravir). Exposure is dispensing of an eligible oral antiviral on day 0; the comparator is no qualifying day-0 initiation. The JMDC insurer claims database is used.
Key exclusion criteria
Hospitalised on day 0. An acute COVID-19 diagnosis in the prior 180 days. Not continuously enrolled from day -365 through day 0. Only suspected-flag records. An empty drug-specific eligibility set (a claims-identifiable contraindication or contraindicated co-medication for all three oral antivirals).
Target sample size
758000
Research contact person
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
kutsuna@hp-infect.med.osaka-u.ac.jp
Public contact
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
kutsuna@hp-infect.med.osaka-u.ac.jp
Sponsor or person
Institute
The University of Osaka, Graduate School of Medicine Faculty of Medicine
Institute
Department
Personal name
Funding Source
Organization
The University of Osaka
Organization
Division
Category of Funding Organization
Self funding
Nationality of Funding Organization
Japan
Other related organizations
Co-sponsor
None
Name of secondary funder(s)
None
IRB Contact (For public release)
Organization
The University of Osaka Hospital, Ethical Review Board
Address
2-15, Yamadaoka, Suita city
Tel
0836-6879-5111
rinri@hp-crc.med.osaka-u.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
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
Other administrative information
Date of disclosure of the study information
| 2026 | Year | 09 | Month | 01 | Day |
Related information
URL releasing protocol
Publication of results
Unpublished
Result
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
Progress
Recruitment status
Preinitiation
Date of protocol fixation
| 2026 | Year | 04 | Month | 14 | Day |
Date of IRB
| 2026 | Year | 04 | Month | 14 | Day |
Anticipated trial start date
| 2026 | Year | 09 | Month | 01 | Day |
Last follow-up date
| 2027 | Year | 03 | Month | 31 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
This is a target trial emulation using the JMDC insurer claims database (day-0 new-user design with propensity-score overlap weighting and IPCW). Initiating an oral antiviral on the day of outpatient COVID-19 diagnosis is compared with not initiating, estimating the risk of newly recorded subacute post-COVID symptoms during days 29-60. Eligible patients are adults aged 18 or older with a confirmed COVID-19 diagnosis between April 2024 and March 2025. Anticipated ~758,000 eligible patients (~58,000 treated) and ~7,300 events. This is a prospective (pre-analysis) registration performed before viewing any treatment effect. Transparency statement: the outcome definition was developed after observing a null result of a prior analysis of the same cohort (protocol v0.3; a high-specificity post-COVID condition outcome over days 70-180, RR 1.12), so its origin is post hoc; however, the definition was selected using the attributable fraction relative to each patient own pre-infection background rate (a treatment-independent quantity) without linking any candidate outcome to treatment status. Existing anonymized data are analysed after institutional review board approval.
Management information
Registered date
| 2026 | Year | 09 | Month | 01 | Day |
Last modified on
| 2026 | Year | 09 | Month | 01 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071861
