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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 6 April 2020
Main ID:  EUCTR2018-003524-36-IE
Date of registration: 05/11/2019
Prospective Registration: Yes
Primary sponsor: UMC Amsterdam location AMC
Public title: Randomized, mulitcenter study to investigate how infliximab dosing calculated by a computer compares to the standard dosing during the induction of infliximab in patients with severe colitis ulcerosa.
Scientific title: Randomized, Multicenter Study to Investigate the Efficacy of Dashboard Driven Individualized Dosing of Infliximab Compared To Standard Dosing During the Induction in Patients with Acute Severe Ulcerative Colitis - TITRATE
Date of first enrolment: 25/03/2020
Target sample size: 124
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003524-36
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: yes
Other specify the comparator: same medicinal substance but as standard dosing
Number of treatment arms in the trial: 2
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes
Countries of recruitment
Ireland Netherlands
Contacts
Name: IBD trial office   
Address:  Meibergdreef 9 1105 AZ Amsterdam Netherlands
Telephone: 0031205651125
Email: ibdstudies@amc.uva.nl
Affiliation:  UMC Amsterdam location AMC
Name: IBD trial office   
Address:  Meibergdreef 9 1105 AZ Amsterdam Netherlands
Telephone: 0031205651125
Email: ibdstudies@amc.uva.nl
Affiliation:  UMC Amsterdam location AMC
Key inclusion & exclusion criteria
Inclusion criteria:
1. Adult UC patients (=18 years)
2. Admission with acute severe UC (defined patients with bloody diarrhoea = 6/day and any signs of systemic toxicity (pulse > 90/min, temperature > 37.8°C, haemoglobin < 105 g/l, erythrocyte sedimentation rate [ESR] > 30 mm/h, or C-reactive protein [CRP] > 30 mg/l)
3. Failure to intravenous steroid treatment as defined by the Oxford criteria (more than 8 stools/d or 3-8 stools/d and CRP=45 on day 3 after starting iv steroid treatment)
4. Patients going through baseline endoscopy and biopsy sampling (including CMV) before starting on IFX treatment
5. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
6. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
7. Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion criteria:
1. Patients at imminent need of surgery as judged by the treating clinician
2. Previous use of IFX
3. Enteric pathogens (such as Salmonella, Shigella, Yershinia, Campylobacter and C. difficile) detected by stool analysis within 2 weeks prior to enrollment or at screening
4. Active participation in another interventional trial
5. Patients with Crohn’s disease or IBD-U
6. Patients with abdominal abscess
7. Patients with colonic stricture
8. Patients with a history of colon cancer or colonic dysplasia, unless sporadic adenoma, which has been removed
9. Active or latent tuberculosis (screening according to national guidelines)
10. Cardiac failure in NYHA stage III-IV
11. History of demyelinating disease
12. Recent live vaccination
13. Patients with ongoing acute/chronic infection (including but not limited to HIV, hepatitis B and C) with the exception of chronic herpes labialis or cervical HPV
14. History of cancer in the last 5 years with the exception of non-melanoma skin cancer
15. A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures
16. Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures
17. Patients unable to attend all study visits
18. Patients with a history of non-compliance with clinical study protocols
19. Contraindication for endoscopy
20. Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer
21. Patients who received cyclosporine in the previous 14 days
22. Pregnancy and lactation



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
Ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Intervention(s)

Trade Name: Remicade
Product Name: NA
Product Code: NA
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 90-

Trade Name: Metoject
Pharmaceutical Form:
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE DISODIUM
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 25-

Trade Name: Puri-Nethol
Pharmaceutical Form: Tablet
INN or Proposed INN: MERCAPTOPURINE
CAS Number: 50-44-2
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: up to
Concentration number: 2.5-

Trade Name: Remsima
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 90-

Trade Name: Inflectra
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 90-

Trade Name: Flixabi
Pharmaceutical Form: Powder for concentrate and solution for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 90-

Primary Outcome(s)
Main Objective: The objective of this study is to investigate whether intensive, personalized IFX dosing by using a pharmacokinetics driven dashboard system during the induction phase in patients with acute severe UC leads to increased treatment success (as defined by sustained clinical response and endoscopic response at week 6) as compared to the standard dosing.
Primary end point(s): Treatment success at week 6, defined as a combination of
• clinical response (defined as a Lichtiger score of < 10 points with a decrease of at least 3 points compared to baseline) AND
• endoscopic response (defined as a decrease of at least 2 points in the UCEIS at week 6 endoscopy compared to baseline)
Secondary Objective: -Proportion of patients in remission at week 6 and 26 as measured by the Mayo score
-Proportion of patients with response at week 6 and 26 as measured by the Mayo score
-Proportion of patients in clinical remission at week 6 and 26 as measured by the Simple Clinical Colitis Activity Index
-Proportion of patients in corticosteroid-free remission at week 26 as measured by the Simple Clinical Colitis Activity Index
-Proportion of patients with clinical remission measured by the Lichtiger scale at week 6 and 26
-Proportion of patients in biochemical remission at week 6 and 26
-Proportion of patients with endoscopic response as measured by the Mayo endoscopic subscore
-Proportion of patients with endoscopic remission at week 6 and 26 as measured by the UCEIS
-Proportion of patients with mucosal healing at week 6 and 26 as measured by the Mayo endoscopic subscore
-Proportion of patients with complete mucosal healing at week 6 and 26




Timepoint(s) of evaluation of this end point: Week 6
Secondary Outcome(s)
Secondary end point(s): - Proportion of patients in remission at week 6 and 26 as measured by the Mayo score (Mayo score = 2 with no individual subscore >1)
- Proportion of patients with response at week 6 and 26 as measured by the Mayo score (decrease in Mayo score = 3 points and =30% from baseline and a decrease in the rectal bleeding subscore =1 or an absolute rectal bleeding subscore of 0 or 1)
- Proportion of patients in clinical remission at week 6 and 26 as measured by the Simple Clinical Colitis Activity Index (SCCAI score = 2)
- Proportion of patients in corticosteroid-free remission at week 26 as measured by the Simple Clinical Colitis Activity Index (SCCAI score = 2)
- Proportion of patients with clinical remission measured by the Lichtiger scale at week 6 and 26 (Lichtiger score = 3)
-Days in clinical response (defined as Lichtiger score of <10 points with a decrease of at least 3 points compared to baseline) and remission ( defined as Lichtiger score < 3) throughout week 0-6
- Proportion of patients in biochemical remission at week 6 and 26 (CRP = 5.0 mg/L and fecal calprotectin < 250 mg/g)
- Proportion of patients with endoscopic response as measured by the Mayo endoscopic subscore (=1 point improvement) at week 6 and 26
- Proportion of patients with endoscopic remission measured by the UCEIS (UCEIS 1 point on all descriptors)
- Proportion of patients with mucosal healing at week 6 and 26 as measured by the Mayo endoscopic subscore (eMayo 0 or 1)
- Proportion of patients with complete mucosal healing at week 6 and 26 as measured by the Mayo endoscopic subscore (eMayo 0)
- Degree of histological improvement at week 6 and 26 compared to baseline as defined by the Robarts histopathology index
- Proportion of patients reaching minimally clinically important difference in quality of life at week 6 and week 26 compared to baseline as assessed by the IBDQ and EQ-5D-5L questionnaire
- Colectomy rates at week 26
- Total IFX dosing (mg/kg) until week 26
Timepoint(s) of evaluation of this end point: Week 6 and week 26
Secondary ID(s)
2018-003524-36-NL
6746101818
Source(s) of Monetary Support
Pfizer
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 25/03/2020
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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