UMIN-ICDS Clinical Trial

Public title

A real-world study on gradually increasing the dose (incremental reintroduction and desensitization) after side effects from anti-tuberculosis drugs

Acronym

Gradual dose increase for TB drugs

Scientific Title

A retrospective observational study on the real-world practice of low-dose incremental reintroduction and desensitization therapy for anti-tuberculosis drugs using single-center medical records and large-scale medical information databases

Scientific Title:Acronym

Retrospective observational study of TB drug incremental reintroduction and desensitization

Region

Japan

Condition

Tuberculosis

Classification by specialty

Pneumology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To clarify the real-world practice of planned low-dose incremental reintroduction (low-dose incremental reintroduction and desensitization therapy) after the onset of adverse reactions to anti-tuberculosis drugs, using electronic medical record data from NHO Tokyo National Hospital and large-scale medical receipt databases.

Basic objectives2

Others

Basic objectives -Others

Descriptive epidemiology and algorithm validation

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Positive predictive value (PPV) of the pre-fixed SQL extraction algorithm identifying low-dose incremental reintroduction and desensitization therapy based on a history of administration below a specific threshold.

Key secondary outcomes

Exploratory evaluation of sensitivity, specificity, and negative predictive value (NPV) of the SQL extraction algorithm in our validation study. Inter-reviewer agreement (kappa coefficient). Frequency of off-target cases (cases not intended for active tuberculosis treatment). Real-world practices of the therapy in a single center and large-scale medical information databases (JMDC, DeSC) (target drugs, starting dose, increment interval and duration, days to reach maintenance dose, frequency of implementation and prescription patterns, maintenance dose achievement rate, transition rate to alternative drugs, and adverse event recurrence rate). Treatment completion rate or treatment continuation status in our hospital. Exploratory investigation of patient background and drug factors associated with the success or failure of low-dose incremental reintroduction and desensitization therapy.

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

1) Single-center data: Patients aged 18 years or older who visited our hospital between April 1, 2014, and March 31, 2026, with a first-time definitive diagnosis of ICD-10 codes A15-A19, and a history of same-day prescription of 3 or more groups among first-line anti-tuberculosis drugs (INH, RFP/RBT, PZA, EMB/SM). 2) JMDC and DeSC databases: Patients aged 18 years or older with a first-time definitive diagnosis of ICD-10 codes A15-A19, and a history of same-day prescription of 3 or more groups among first-line anti-tuberculosis drugs.

Key exclusion criteria

1) Patients for whom anti-tuberculosis drugs were used for purposes other than active tuberculosis treatment (e.g., non-tuberculous mycobacterial infection, latent tuberculosis infection, prophylactic use). 2) Patients for whom the purpose of anti-tuberculosis drug administration is indeterminate. 3) Patients whose minimum necessary medical records are missing, making it extremely difficult to evaluate the implementation of low-dose incremental reintroduction or desensitization therapy (for single-center data). 4) Patients who refuse to participate in the study.

Target sample size

700

Name of lead principal investigator

1st name	Takafumi
Middle name
Last name	Kato

Organization

NHO Tokyo National Hospital

Division name

Center for Pulmonary Diseases, Clinical Research Center

Zip code

2048585

Address

3-1-1 Takeoka, Kiyose City, Tokyo, Japan

TEL

042-491-2111

Email

kato.takafumi.an@mail.hosp.go.jp

Name of contact person

1st name	Takafumi
Middle name
Last name	Kato

Organization

NHO Tokyo National Hospital

Division name

Center for Pulmonary Diseases, Clinical Research Center

Zip code

2048585

Address

3-1-1 Takeoka, Kiyose City, Tokyo, Japan

TEL

042-491-2111

Homepage URL

Email

kato.takafumi.an@mail.hosp.go.jp

Institute

NHO Tokyo National Hospital

Institute

Department

Personal name

Organization

Japan Society for the Promotion of Science (JSPS)
Japan Agency for Medical Research and Development (AMED)
National Hospital Organization (NHO)

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

NHO Tokyo National Hospital

Address

3-1-1 Takeoka, Kiyose City, Tokyo, Japan

Tel

042-491-2111

Email

kato.takafumi.an@mail.hosp.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2026

Year

05

Month

29

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

05

Month

26

Day

Date of IRB

2026

Year

05

Month

26

Day

Anticipated trial start date

2026

Year

05

Month

29

Day

Last follow-up date

2029

Year

04

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

[Study Design]
This study is a retrospective, non-interventional, observational study (descriptive epidemiological study and algorithm validation study) using single-center electronic medical records and large-scale domestic medical information databases (the JMDC hospital database and the DeSC database).

[Patient Recruitment and Period]
Single-center data: Cases meeting the inclusion criteria (aged 18 or older, first definitive diagnosis of ICD-10 codes A15-A19, and history of same-day prescription of 3 or more groups of first-line anti-tuberculosis drugs) between April 1, 2014, and March 31, 2026.
External databases (JMDC, DeSC): Cases registered in each database who meet the above inclusion criteria.

[Outcome Measures / Variables]
The following clinical information will be retrospectively collected and measured from each data source:
1) Patient characteristics (age, sex, medical history, concomitant drugs, etc.) 2) Tuberculosis-related clinical information (treatment start date, initial regimen, etc.) 3) Adverse event information (type of side effects, onset date, laboratory values, etc.) 4) Information on low-dose incremental reintroduction and desensitization therapy (target drugs, starting dose, increment intervals, increment duration, date of reaching maintenance dose, etc.) 5) Clinical outcomes (success or failure of reaching maintenance dose, transition rate to alternative drugs, recurrence rate of adverse events, treatment completion status, etc.)

[Supplementary Information on Dates]
Since this study is a retrospective observational study using existing clinical data and does not involve prospective patient enrollment, the clinical trial dates are defined and entered as follows:
Date of protocol fixation: Date of IRB approval
Anticipated trial start date: Anticipated date of starting data collection (medical record review/extraction)
Last follow-up date: The final day of the research period approved by the IRB

Registered date

2026

Year

05

Month

29

Day

Last modified on

2026

Year

05

Month

29

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000070659