UMIN-CTR Clinical Trial

Public title

Epidemiology of Clostridium difficile infection in Japan

Acronym

CDI-Japan

Scientific Title

Epidemiology of Clostridium difficile infection in Japan

Scientific Title:Acronym

CDI-Japan

Region

Japan

Condition

Clostridium difficile infection (CDI)

Classification by specialty

Infectious disease

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

1. To determine the incidence of CDI in selected hospitals in Japan
2. To describe CDI population characteristics, management and outcome
3. To compare performance of nucleic acid amplification test (NAAT), toxigenic culture and the standard laboratory tests used in Japanese hospitals
4. To describe molecular epidemiology of CDI in Japan and antibiotic resistance of C. difficile isolates

Basic objectives2

Others

Basic objectives -Others

Epidemiology

Trial characteristics_1

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

1. Incidence of CDI
Incidence of CDI will be measured as the number of positive C. difficile tests (by any test) per 10,000 patient-days (pd) in the study wards
Attempts will be made to assess the relationship between incidence of CDI and
(a) testing density (measured as the number of test per 10,000 pd)
(b) the C. difficile laboratory tests used
(c) the ward/population type

2. CDI population characteristics, management and outcome
CDI population characteristics will be described and compared to the non CDI population
The management of CDI will be described together with the status of the patients 60 days after the onset of the disease to assess morbidity/mortality. The 60 days outcome of CDI patient will be compared to the one of non CDI patients to assess CDI related morbidity

3. Performance of NAAT, toxigenic culture and the standard laboratory tests performed in hospitals in Japan
Test results will be compared across the 3 C. difficile tests performed (in hospital laboratory or in NIID). Characteristics of individual with discrepant results and their 60 days post CDI outcome will also be described.

4. Molecular epidemiology of CDI and antibiotic susceptibility of C. difficile recovered from hospitalized patients in Japan

Typing analysis and antibiotic susceptibility testing will be performed and described.

Key secondary outcomes

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

All patients who newly develope clinically significant diarrhea in the study wards and who provide written consent are eligible for inclusion.

Key exclusion criteria

None

Target sample size

1000

Name of lead principal investigator

1st name	Haru
Middle name
Last name	Kato

Organization

National Institute of Infectious Diseases

Division name

Department of Bacteriology II

Zip code

2080011

Address

Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan

TEL

+81-42-561-0771

Email

cato@nih.go.jp

Name of contact person

1st name	Haru
Middle name
Last name	Kato

Organization

National Institute of Infectious Diseases

Division name

Department of Bacteriology II

Zip code

2080011

Address

Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan

TEL

+81-42-561-0771

Homepage URL

Email

cato@nih.go.jp

Institute

National Institute of Infectious Diseases

Institute

Department

Personal name

Organization

Sanofi Pasteur

Organization

Division

Category of Funding Organization

Outside Japan

Nationality of Funding Organization

France

Co-sponsor

Name of secondary funder(s)

Organization

National Institute of Infectious Diseases

Address

Toyama 1-23-1, Shinjuku, Tokyo, Japan

Tel

03-5285-1111

Email

not available

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

八戸市立市民病院（青森県）
国立病院機構東京医療センター（東京都）
亀田総合病院（千葉県）
東京ベイ・浦安市川医療センター（千葉県）
豊川市民病院（愛知県）
東海中央病院（岐阜県）
国立病院機構刀根山病院（大阪府）
奈良県立医科大学附属病院（奈良県）
国立病院機構呉医療センター、中国がんセンター（広島県）
下関市立市民病院（山口県）
産業医科大学病院（福岡県）
沖縄県立南部医療センター・こども医療センター（沖縄県）

Date of disclosure of the study information

2014

Year

10

Month

03

Day

URL releasing protocol

Not applicable

Publication of results

Published

URL related to results and publications

https://www.sciencedirect.com/science/article/abs/pii/S1075996419300460?via%3Dihub

Number of participants that the trial has enrolled

566

Results

The overall incidence of CDI was 7.4/10,000 patient-days, and the testing frequency and CDI incidence rate were highly correlated. Numerous patients with CDI are being overlooked due to inadequate testing in Japan. Risk factors for CDI in Japan were similar to those identified in the US and Europe. The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile were lower than most previous reports. Also, this study found low PPV of EIAs for toxins.

Results date posted

2019

Year

10

Month

21

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

A prospective cohort study of Clostridioides difficile infection (CDI) was conducted from May 12, 2014 to May 11, 2015 at 12 medical facilities (20 wards) located throughout 11 prefectures in Japan. Stool specimens were collected from patients 18 years of age or older with clinically significant diarrhea (CSD), who provided consent to participate. CSD was defined by one of the following conditions; 1) at least 3 diarrheal bowel movements (Bristol stool chart grade 6-7) in the previous 24 hours, or a diarrheal bowel movement with abdominal pain and/or cramping; 2) among patients with pre-existing chronic diarrhea, an increase of >= 3 diarrheal stools compared with the usual diarrheal frequency; 3) or the same frequency of diarrhea with new or worsening abdominal pain and/or cramping. CDI was defined by positive result on enzyme immunoassay for toxins A/B (EIA), nucleic acid amplification test for the toxin B gene (NAAT) or toxigenic culture (TC).

Participant flow

Of the 636 CSD episodes in 566 patients enrolled, 173 (27.2%) met study criteria for CDI. Eleven patients had multiple CDI episodes, three of whom had a new episode while eight experienced a recurrence. Of the 566 patients, a total of 152 patients received the diagnosis of CDI at the first enrollment.

Adverse events

Not applicable

Outcome measures

Not applicable

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2014

Year

03

Month

21

Day

Date of IRB

2013

Year

03

Month

14

Day

Anticipated trial start date

2014

Year

05

Month

12

Day

Last follow-up date

2016

Year

07

Month

12

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

2019

Year

10

Month

03

Day

Other related information

Treatment and management of study participants will be based on the results of the local standard of laboratory tests performed at each hospital and assessment of the attending physician. Hospital test results, diagnosis and treatment data will be abstracted and collected.
The status of all patients tested for diarrhea (whatever the results from the laboratory test are) will be assessed through calling the patients or their caregivers, 60 days after the date of the stool sampling.

Registered date

2014

Year

10

Month

03

Day

Last modified on

2019

Year

10

Month

23

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017822