UMIN-ICDS Clinical Trial

Public title

A study of whether prescribing oral doxycycline or minocycline after an asymptomatic tick bite reduces the risk of developing Japanese spotted fever on days 3-14, using health insurance claims data (target trial emulation)

Acronym

Tick-bite JSF TTE Study (JMDC)

Scientific Title

Oral doxycycline or minocycline prescribing after tick bite and incident Japanese spotted fever: a target trial emulation using the JMDC claims database

Scientific Title:Acronym

Japanese Spotted Fever Prophylactic Prescribing TTE Study (JMDC)

Region

Japan

Condition

Tick bite (asymptomatic outpatient visit). The outcome is Japanese spotted fever (Rickettsia japonica infection).

Classification by specialty

Infectious disease

Dermatology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Using the JMDC claims database, to estimate whether, among asymptomatic patients presenting to outpatient care with a new tick bite, a policy of prescribing oral doxycycline or minocycline at time zero (Day 0) reduces the day 3-14 risk of Japanese spotted fever diagnosis, compared with a policy of prescribing no systemic antibiotic at Day 0, within a target trial emulation framework. Database-specific propensity-score stabilized IPTW is used to estimate standardized 14-day risk differences and risk ratios (prescription-policy effect; facility-cluster 95% CI). This registration is performed before analysis and without reference to outcomes.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

A new, non-suspect Japanese spotted fever diagnosis recorded during days 3-14 after time zero (Day 0). Database-specific propensity-score stabilized IPTW is used to estimate standardized 14-day risks, risk differences, and risk ratios (facility-cluster 95% CI). The assessment window is set to days 3-14 to align time zero with the incubation period of Japanese spotted fever (approximately 2-8 days).

Key secondary outcomes

Secondary: (1) evaluating doxycycline and minocycline separately to explore heterogeneity of effect between drugs; (2) exploring effect modification by age, sex, season, region, facility characteristics, and immunosuppressive status; (3) assessing robustness to the outcome definition, assessment window, comparator, confounding-adjustment method, and within-facility comparison; and (4) assessing residual confounding and misclassification using positive and negative control outcomes and quantitative bias analysis.

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

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) Patients of all ages receiving outpatient care in Japan for a newly recorded tick bite. (2) At least 365 days of observability before time zero (Day 0). (3) No recorded tick bite in the prior 90 days. (4) No Japanese spotted fever on Day 0 or in the prior 30 days. (5) No fever, rash, hospitalization, or severe-infection signs on Day 0 (asymptomatic). (6) No contraindication to the target drugs (oral doxycycline or minocycline) and no clear treatment indication from another condition. Hokkaido is excluded if regional information is available. The main analysis uses only the first eligible episode per patient. The study period for the insurer database is April 2012 to December 2025.

Key exclusion criteria

(1) Fever, rash, hospitalization, or severe-infection signs on Day 0 (symptomatic). (2) A recorded tick bite in the prior 90 days. (3) Japanese spotted fever on Day 0 or in the prior 30 days. (4) Less than 365 days of observability. (5) A contraindication to the target drugs or a clear treatment indication from another condition. (6) Hokkaido, when the region is identifiable. (7) In the main analysis, patients whose follow-up to Day 14 cannot be ensured (numbers and reasons reported by group).

Target sample size

10000

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.med.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.med.osaka-u.ac.jp

Institute

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

Institute

Department

Personal name

Organization

The University of Osaka

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

None

Name of secondary funder(s)

None

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

08

Month

07

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

04

Month

14

Day

Date of IRB

2026

Year

04

Month

14

Day

Anticipated trial start date

2026

Year

08

Month

07

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 related information

This is a target trial emulation (retrospective cohort) using the JMDC claims database (insurer database, study period April 2012 to December 2025; applicability of the late-elderly database to be determined after reviewing its specifications). Among asymptomatic patients presenting to outpatient care with a new tick bite, a Day 0 policy of oral doxycycline or minocycline is compared with a policy of no systemic antibiotic, and the day 3-14 risk of Japanese spotted fever is estimated using database-specific propensity-score stabilized IPTW. This is a prospective registration before analysis and without reference to outcomes. Existing anonymized data are analysed after institutional review board approval.

Registered date

2026

Year

08

Month

07

Day

Last modified on

2026

Year

08

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071558