UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A comparative study of the efficacy of tacrolimus with infliximab in intractable ulcerative colitis
Title of the study (Brief title)	A comparison of the efficacy of tacrolimus with infliximab in ulcerative colitis
Region	Japan

Condition
Condition	Ulcerative colitis
Classification by specialty	Gastroenterology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the efficacy of tacrolimus over infliximab in steroid-resistant or -dependent ulcerative colitis with moderate to severe activity.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase IV

Assessment
Primary outcomes	Clinical response rate at week 10 according to the DAI score.
Key secondary outcomes	Clinical remission rate at week 10 DAI score at week 10 Endoscopic remission rate at week 10

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Tacrolimus will be administered orally for 10 weeks at the trough level of 10-15 ng/ml for the first 2 weeks following that of 5-10 ng/ml for the rest of the study period.
Interventions/Control_2	Infliximab will be administered intravenously at the dose of 5 mg/kg at 0, 2, 6 weeks.
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	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients who have an established diagnosis of ulcerative colitis and fulfill the criteria as described below: 1. Patients with moderate to severe activity defined by a DAI score of more than or equal to 6, AND an endoscopic sub-score of more than or equal to 2. 2. Patients showing steroid-resistance or steroid-dependence defined as below. 1) Steroid-resistance: No symptomatic improvement despite administration of oral prednisolone >= 30 mg for 2 weeks or i ntravenous prednisolone >= 30 mg for 1 week. 2) Steroid-dependence: Symptomatic worsening during steroid tapering or following discontinuation of steroids within 12 months.
Key exclusion criteria	1. Patients with only proctitis. 2. Patients having contraindications to tacrolimus including current use of cyclosporine, bozentan, or potassium-sparing diuretics. 3. Patients having contraindications to infliximab including serious infection (sepsis), active tuberculosis infection, allergy to murine-derive proteins. 4. Patients who have been administered anti-TNF agents, tacrolimus, or cyclosporine. 5. Concomitant medication: 1) Changed the dose of oral 5-aminosalicylate (ASA) agents within 1 week. 2) Used topical 5-ASA agents or topical steroid agents within 1 week. 3) Underwent cytapheresis within 1 week. 4) Started an immunomodulator (azathioprine, mercaptopurine) within 12 weeks or changed the dose of the agent within 4 weeks. 5) Changed the dose of oral prednisolone within 1 week. 6) Changed the dose of intravenous prednisolone within 1 week. 6. Patients who have a serious infection or are suspected to have it. 7. Patients who have a serious cardiovascular disease. 8. Patients who have a serious renal disease (Serum Cr >= 2.0 mg/dl) 9. Patients who have a serious hepatic disease (Total bilirubin >= 3.0 mg/dl or AST or ALT >= 200 IU/ml) 10. Patients who are pregnant, possible to be pregnant, or want to be during the study period, or are breastfeeding. 11. Patients who have a neoplasm or had a neoplasm. 12. Patients who have a psychological disorder. 13. Patients who underwent resection of the colon (excluding appendectomy) 14. Patients who are judged to be exclusive by investigators for a certain reason.
Target sample size	130

Research contact person
Name of lead principal investigator	Toshifumi Hibi
Organization	Kitasato University Kitasato Institute Hospital
Division name	Center for Advanced IBD Research and Treatment
Address	5-9-1 Shirogane, Minato Tokyo
TEL	03-5791-6487
Email	thibi@insti.kitasato-u.ac.jp

Public contact
Name of contact person	Toshifumi Hibi
Organization	Kitasato University Kitasato Institute Hospital
Division name	Center for Advanced IBD Research and Treatment
Address	5-9-1 Shirogane, Minato Tokyo
TEL	03-5791-6487
Homepage URL
Email	thibi@insti.kitasato-u.ac.jp

Sponsor
Institute	Department of Internal Medicine, Division of Gastroenterology and Hepatology, Keio University School of Medicine
Institute
Department

Funding Source
Organization	Research group of intractable inflammatory bowel disease subsidized by the Ministry of Health, Labour and Welfare of Japan
Organization
Division
Category of Funding Organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

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

愛知医科大学 (愛知県)、秋田赤十字病院 (秋田県)、旭川医科大学 (北海道)、大船中央病院 (神奈川県)、大阪市立十三市民病院 (大阪府)、大阪市立大学 (大阪府)、鹿児島大学 (鹿児島県)、金沢大学 (石川県)、関西医科大学 (大阪府)、京都大学 (京都府)、京都府立大学 (京都府)、九州大学 (福岡県)、慶應義塾大学 (東京都)、滋賀医科大学 (滋賀県)、札幌厚生病院 (北海道)、島根大学 (島根県)、社会保険中央総合病院 (東京都)、昭和大学横浜市北部病院 (神奈川県)、東京医科歯科大学 (東京都)、東京慈恵会医科大学 (東京都)、東京女子医科大学・消化器内科 (東京都)、東京女子医科大学・第二外科 (東京都)、東京大学・腫瘍外科 (東京都)、東邦大学医療センター佐倉病院 (千葉県)、東北大学 (宮城県)、名古屋大学 (愛知県)、名古屋市立大学 (愛知県)、浜松南病院 (静岡県)、兵庫医科大学 (兵庫県)、弘前病院 (青森県)、弘前大学医学部 (青森県)、広島大学 (広島県)、福岡大学筑紫病院 (福岡県)、藤田保健衛生大学 (愛知県)、防衛医科大学校 (埼玉県)、横浜市立大学市民医療センター (神奈川県)、琉球大学 (沖縄県)、和歌山県立医科大学 (和歌山県)、群馬大学 (群馬県)、北里大学北里研究所病院 (東京都)、東海大学八王子病院 (東京都)、横浜市立大学 (神奈川県)、埼玉医科大学 (埼玉県)、横浜市民病院 (神奈川県)、大阪府済生会中津病院 (大阪府)、岡山大学 (岡山県)、新潟大学 (新潟県)、埼玉メディカルセンター (埼玉県)

Other administrative information
Date of disclosure of the study information	2013 Year 05 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 02 Month 25 Day
Anticipated trial start date	2013 Year 05 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2013 Year 04 Month 29 Day
Last modified on	2016 Year 10 Month 31 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000012376