UMIN-CTR Clinical Trial

Public title

Construction of therapeutic evidence for active ulcerative colitis requiring hospitalization

Acronym

Construction of therapeutic evidence for active ulcerative colitis requiring hospitalization

Scientific Title

Construction of therapeutic evidence for active ulcerative colitis requiring hospitalization

Scientific Title:Acronym

None

Region

Japan

Condition

ulcerative colitis

Classification by specialty

Gastroenterology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To confirm the short-term usefulness and safety of therapeutic agents for patients with active ulcerative colitis who are hospitalized and have moderate or higher disease.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

On December 27, 2022, the evaluation items were fixed as follows.
Clinical remission rate at Day 7 and Day 14

Key secondary outcomes

On December 27, 2022, the evaluation items were fixed as follows.

1 Clinical improvement rate on days 7 and 14
2 Difference between baseline and PRO on Days 3, 7, and 14
3 Surgery rate within 28 days
4 Proportion of cases in which treatment was changed within 28 days
5 Infectious disease that developed within 28 days
6 Adverse effects other than infections that developed within 28 days

For the above, we evaluated the efficacy and safety of steroids, the first advanced therapy after hospitalization, and the second advanced therapy, divided into acute severe UC, severe, and moderate.
In addition, the remission rate, improvement rate, treatment change rate, and surgery rate of steroid use cases and advanced therapy were evaluated separately for steroid use cases and non-use cases before hospitalization.

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

16

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients who met the criteria for ulcerative colitis
2) Inpatients who have a diagnosis criteria at the time of enrollment and have moderate or severe activity
3) Patients who will be treated with steroids, GMA, Tacrolimus, anti-ANF agents, Tofacitinib, vedolizumab, or ustekinumab
4) Patients over 16 years old
5)Patients who have contents for this study

Key exclusion criteria

1) Outpatients
2) Colitis other than ulcerative colitis (e.g. infectious colitis)
3) Patients who will receive total colectomy
4) Patients judged to be inappropriate for inclusion in this study
5) Patients participate other clinical trial.

Target sample size

300

Name of lead principal investigator

1st name	Makoto
Middle name
Last name	Naganuma

Organization

Kansai Medical University

Division name

Department of Gastroenterology and Hepatology

Zip code

573-1010

Address

2-5-1 Shinmachi, Hirakata City

TEL

072-804-0101

Email

naganuma@hirakata.kmu.ac.jp

Name of contact person

1st name	Makoto
Middle name
Last name	Naganuma

Organization

Kansai Medical University

Division name

Department of Gastroenterology and Hepatology

Zip code

573-1010

Address

2-5-1 Shinmachi, Hirakata City

TEL

072-804-0101

Homepage URL

Email

naganuma@hirakata.kmu.ac.jp

Institute

Kansai Medical University

Institute

Department

Personal name

Organization

Kansai Medical University

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Kansai Medical University

Address

2-5-1, Shinmachi, Hirakata-City

Tel

072-804-2551

Email

kmuccr@hirakata.kmu.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

杏林大学医学部　第三内科学
東邦大学医療センター佐倉病院 消化器内科
慶應義塾大学医学部　消化器内科
東京慈恵会医科大学 内科学講座 消化器・肝臓内科
札幌医科大学医学部　消化器内科学講座　　
北里大学北里研究所病院　炎症性腸疾患先進治療センター
大阪医科大学　炎症性腸疾患センター
東京医科歯科大学医学部附属病院　臨床試験管理センター
福岡大学医学部付属病院　消化器内科
防衛医科大学校　消化器内科
岩手医科大学医学部 内科学講座消化器内科消化管分野
大阪大学大学院　医学系研究科　消化器内科学
佐賀大学医学部附属病院 消化器内科
公益財団法人慈愛会 いづろ今村病院
東京女子医科大学消化器病センター
東北大学病院　消化器内科
千葉大学附属病院　消化器内科
横浜市立大学附属市民総合医療センターIBDセンター
弘前大学大学院医学研究科消化器血液内科学講座
愛知医科大学病院　消化管内科
浜松医科大学内科学第一講座
辻中病院柏の葉　消化器内科
札幌厚生病院　IBDセンター
広島大学大学院　医歯薬保健学研究科　内視鏡医学
京都府立医科大学大学院医学研究科消化器内科学
岡山大学病院　消化器内科・炎症性腸疾患センター
旭川医科大学　内科学講座 病態代謝・消化器・血液腫瘍制御内科学分野（消化器・内視鏡学部門）
久留米大学医学部内科学講座消化器内科部門
東京山手メディカルセンター　炎症性腸疾患内科
兵庫医科大学　炎症性腸疾患内科
済生会中央病院　消化器内科
横浜市立市民病院　消化器内科
金沢大学附属病院　消化器内科
北里大学医学部　消化器内科
栃木県済生会宇都宮病院消化器内科
東京医療センター消化器内科
埼玉医科大学総合医療センター　消化器内科
奈良県立医科大学附属病院 消化器内科
滋賀医科大学消化器内科
宮崎大学　消化器内科
島根大学内科学講座第二
山口大学第一内科
埼玉医科大学消化管内科
国際医療福祉大学三田病院消化器センター
大阪市立大学大学院医学研究科 消化器内科学

Date of disclosure of the study information

2020

Year

07

Month

10

Day

URL releasing protocol

https://link.springer.com/article/10.1007/s00535-023-02048-w

Publication of results

Published

URL related to results and publications

https://link.springer.com/article/10.1007/s00535-023-02048-w

Number of participants that the trial has enrolled

300

Results

Most first-use advaned therapy (ATs) were effective for patients with Acute severe, while second-use ATs might have had limited benefits in inducing clinical remission. These findings may contribute to considerations for the management of hospitalized patients.

Results date posted

2024

Year

01

Month

11

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Hospitalized patients with UC from 39 institutions were prospectively enrolled in this study between August 2020 and July 2021. The data of hospitalized patients who required medical treatment due to exacerbation of clinical symptoms were collected.

Participant flow

Hospitalizations owing to other diseases were excluded. Patients meeting all of the following criteria were enrolled: UC diagnostic criteria according to the Japanese Research Group for Intractable Inflammatory Bowel Disorders, Ministry of Health, Labour, and Welfare; Hospitalized patients owing to disease aggravation of UC; Patients who would use CS, apheresis (CAP), TAC, IFX, adalimumab (ADA), golimumab (GLM), TOFA, VED, UST, or CSA after admission and throughout hospitalization; and 4)patients aged more than 16 years. Patients meeting one of the following criteria were excluded:outpatients;those having colitis other than UC (infectious or ischaemic colitis);those who underwent or had already undergone colectomy; and those participating in clinical trials of other drugs.

Adverse events

A total of 71 AEs were observed in patients with ASUC, including 53 during first-line treatment and 18 during second-line treatment. Infection was observed in 39 cases. Cytomegalovirus (CMV) reactivation and Clostridioides difficile infection (CDI) occurred in 21 and nine cases, respectively. CMV reactivations were diagnosed by serology (n=15), histology (n=2) or both (n=4). Most CMV reactivation (16/21, 76.1%) and CDI (6/8, 75.0%) were found in patients receiving CS. Seven cases had catheter-related bloodstream infections. Non-infected AEs were observed in 32 cases. Six of the seven renal dysfunction cases occurred in the TAC group. All renal dysfunction cases had elevated serum creatinine levels, and all patients recovered by reducing the TAC dose. Nine patients had liver dysfunction. Occurrence or exacerbation of diabetes was observed in four patients who received a daily CS dose >40 mg. For cardiovascular disease, deep vein thrombosis (DVT) occurred in two cases, and pulmonary embolism occurred in one patient. All patients were treated with anticoagulants, and none died. No pneumonia, tuberculosis, or death was observed in this cohort.

Outcome measures

We evaluated the clinical efficacy of each treatment in hospitalized patients with ASUC. The primary endpoint was the rate of CR at Day 7 and 14 in patients who were treated with CS, first AT, and second AT. CR was defined as PRO2 <2 with no blood in the stool. Patients requiring alternative treatments or colectomy were defined as those with no CR. The main secondary endpoints were the clinical improvement (CI) rate on Day 7 and 14 and the proportion of patients requiring colectomy within 28 days. CI was defined as a decrease of at least 50% in PRO2. These outcomes were assessed in patients within the following groups; 1) patients who received CS as the first-line treatment immediately after hospitalization; 2) patients who received any ATs without additional CS as the first-line treatment immediately after hospitalization; 3) patients who received ATs owing to CS refractoriness; and 4) patients who received second ATs throughout their hospitalizations
We also evaluated the difference in treatment selection (CS or AT) and therapeutic effects depending on the presence or absence of steroid use before hospitalization.
The difference in PRO2 on day 0 from PRO2 on Day 3, 7, and 14 was also assessed in patients with CS or each AT. For safety analysis, the number and type of AEs were assessed.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2020

Year

06

Month

30

Day

Date of IRB

2020

Year

07

Month

09

Day

Anticipated trial start date

2020

Year

07

Month

10

Day

Last follow-up date

2022

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This study is currently ongoing, but there are no plans for monitoring/auditing because of observational study

Registered date

2020

Year

07

Month

10

Day

Last modified on

2024

Year

01

Month

11

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046896