UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000062526 |
|---|---|
| Receipt number | R000071574 |
| Scientific Title | Comparative 90-Day Cardiovascular Outcomes After Nirmatrelvir/Ritonavir, Molnupiravir, or Ensitrelvir Initiation in Older Outpatients With COVID-19: An Active-Comparator Initiator Study |
| Date of disclosure of the study information | 2026/08/09 |
| Last modified on | 2026/08/09 15:33:31 |
* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments
Basic information
Public title
A study comparing the 90-day risk of cardiovascular events (hospitalization for myocardial infarction, heart failure, or stroke) after initiation of oral antivirals (nirmatrelvir/ritonavir, molnupiravir, or ensitrelvir) among older outpatients with COVID-19
Acronym
Antiviral Cardiovascular Outcomes Comparison Study (JMDC)
Scientific Title
Comparative 90-Day Cardiovascular Outcomes After Nirmatrelvir/Ritonavir, Molnupiravir, or Ensitrelvir Initiation in Older Outpatients With COVID-19: An Active-Comparator Initiator Study
Scientific Title:Acronym
COVID-19 Antiviral Cardiovascular Comparison Study (Late-Elderly)
Region
| Japan |
Condition
Condition
COVID-19 (outpatient episodes in late-elderly adults). The outcome is cardiovascular events (hospitalization for acute myocardial infarction, heart failure, or stroke).
Classification by specialty
| Cardiology | Infectious disease | Geriatrics |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
Using JMDC-provided Japanese late-elderly claims data, to compare 90-day cardiovascular outcomes after initiation of oral antivirals (nirmatrelvir/ritonavir, molnupiravir, or ensitrelvir) among older outpatients with COVID-19. Three pairwise comparisons are conducted in an active-comparator initiator design, with the average treatment effect in the clinical overlap-weighted population as the primary estimand.
Basic objectives2
Safety
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Pragmatic
Developmental phase
Not applicable
Assessment
Primary outcomes
Hospitalization for acute myocardial infarction, heart failure, or stroke (composite) on days 1-90 after antiviral initiation. Overlap-weighted Aalen-Johansen cumulative risks incorporating a prespecified common-across-outcomes censoring model are estimated, with death as a competing event. The three primary pairwise comparisons report risk ratios and risk differences using Bonferroni-adjusted 98.33% confidence intervals.
Key secondary outcomes
Secondary: analyses restricted to a facility-calendar common-support (overlap) population, negative-control outcomes (e.g., fracture) with FDR assessment, analyses of individual cardiovascular components, subgroups by baseline characteristics, and sensitivity analyses. Three pairwise comparisons (A1: molnupiravir vs nirmatrelvir/ritonavir; A2: molnupiravir vs ensitrelvir; A3: nirmatrelvir/ritonavir vs ensitrelvir).
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
| 75 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
Outpatient COVID-19 episodes in JMDC-provided Japanese late-elderly claims data in which one of the target oral antivirals (nirmatrelvir/ritonavir, molnupiravir, or ensitrelvir) was initiated on the diagnosis day or the following day. Initiation from July 1, 2023, through December 31, 2024, with follow-up through March 31, 2025. Pairwise analyses required claims-observable eligibility for both drugs and exactly one comparator initiated on the diagnosis day or the following day. A 365-day baseline window was ensured.
Key exclusion criteria
None of the three target antivirals initiated on the diagnosis day or the following day. Not meeting claims-observable eligibility for both drugs in a pairwise analysis. More than one comparator drug initiated on the diagnosis day or the following day. Initiation outside the study period.
Target sample size
99289
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 | 08 | Month | 09 | 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
99289
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
Completed
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 | 04 | Month | 14 | Day |
Last follow-up date
| 2026 | Year | 08 | Month | 09 | Day |
Date of closure to data entry
| 2026 | Year | 08 | Month | 09 | Day |
Date trial data considered complete
| 2026 | Year | 08 | Month | 09 | Day |
Date analysis concluded
| 2026 | Year | 08 | Month | 09 | Day |
Other
Other related information
This is a retrospective active-comparator initiator study using JMDC-provided Japanese late-elderly claims data (antiviral initiation July 2023 to December 2024; follow-up through March 2025; 365-day baseline). Among older outpatients with COVID-19, 90-day cardiovascular outcomes after initiation of oral antivirals (nirmatrelvir/ritonavir, molnupiravir, or ensitrelvir) were evaluated in three pairwise comparisons using propensity-score overlap weighting. Existing anonymized data were analysed after institutional review board approval.
Management information
Registered date
| 2026 | Year | 08 | Month | 09 | Day |
Last modified on
| 2026 | Year | 08 | Month | 09 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071574
