A comparison between standard treatment with azathioprine and a modified treatment with a lower dose of azathioprine in combination with allopurinol for patients with inflammatory bowel disease

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2016-004112-35-SE
• Date of registration: 21/06/2017
• Prospective Registration: Yes
• Primary sponsor: SOIBD (The Swedish Organisation for the study of Inflammatory Bowel Diseases)
• Public title: A comparison between standard treatment with azathioprine and a modified treatment with a lower dose of azathioprine in combination with allopurinol for patients with inflammatory bowel disease
• Scientific title: Low-dose azathioprine and allopurinol- versus azathioprine monotherapy in patients with Inflammatory Bowel Disease: An investigator-initiated, open, multicentre, parallel-arm, randomized controlled trial A SOIBD (The Swedish Organisation for the study of Inflammatory Bowel Diseases) study
• Date of first enrolment: 04/04/2018
• Target sample size: 120
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004112-35
• 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: yes Placebo: no Other: no 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

Sweden

Contacts

• Name: Pontus Karling
• Affiliation: SOIBD

• Name: Pontus Karling
• Affiliation: SOIBD

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 18-80 years at the time of inclusion, weight between 50 and 100 kg.

2. Willingness to comply with all trial procedures and being available for the duration of the trial.

3. Clinical and histological verified IBD eligible for treatment with thiopurines due to steroid dependence (failure to taper steroid or starting a second course of systemic steroids within one year) or due to the need for thiopurines for other reasons (disease phenotype, i.e post-surgery decision).

4. A written informed consent to participate in the study is signed before any study-related procedures are performed.

5. A normal TPMT activity measurement (>8.9 U/ml RBC) or normal TPMT genotype (*1/*1).

6. Naïve to thiopurine treatment

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 20

Exclusion criteria:
1. Biologic treatment (anti-TNF, vedoluzimab etc) within the last three months prior the study

2. Concurrent participation in another interventional therapy study.

3. Females who are pregnant or breastfeeding

4. Females of childbearing age and potential who are not willing or capable to use acceptable methods of contraception (oral contraceptives, condoms, diaphragms, intrauterine devices) during the entire study and for up to 3 months after the end-of-study evaluation.
5. Male patients who do not use acceptable barrier methods of contraception (condoms) during the entire course of the study and up to 3 months after the end-of-study evaluation.

6. Inability to follow the treatment protocol (as judged by the investigator)

7. Current treatment with Allopurinol.

8. Patients with gout that needs medical treatment.

9. Estimated GFR < 50 ml/ml

10. Persistent alanine aminotransferase U/L (ALT) above upper limit of the normal range.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with inflammatory bowel diseae (Ulcerative colitis or Crohns disease) wh do not responding to first line therapy

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: Imurel
Product Name: Azathioprine
Product Code: NA
Pharmaceutical Form: Tablet

Trade Name: Allopurinol
Product Name: Allopurinol
Product Code: NA
Pharmaceutical Form: Tablet

Primary Outcome(s)

Secondary Objective: To compare:

Time to remission

Steroid and biologic treatment free remission defined as Clinical remission (HBI =4 or SCCAI =2 ) at week 52 and no need for escalation of IBD therapy.

Clinical response after week 26 and week 52 (defined as ?3 in HBI or ?3 in SCCAI)

The proportion of patients with Fecal calprotectin <200 µg/g (<350 µg/g if Buhlman method is used) at week 26 and 52 .

Quality of life after 52 weeks using Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and short health scale (SHS).

The proportion of patients who reach therapeutics levels of E-6TGN levels (230-450 pmol/L) at week 6 and week 26.

Adverse events defined as any untoward or unfavourable medical occurrence in a human subject

Effects on intestinal permeability and microbiota

Primary end point(s): Steroid and biologic treatment free remission defined as Clinical remission (HBI =4 or SCCAI =2 ) at week 26 and no need for escalation of IBD therapy.

Main Objective: To evaluate the efficacy and safety of low dose azathioprine and allopurinol versus standard azathioprine monotherapy in patients with inflammatory bowel disease.

Timepoint(s) of evaluation of this end point: 26 weeks

Secondary Outcome(s)

Secondary end point(s): To compare:

Time to remission

Steroid and biologic treatment free remission defined as Clinical remission (HBI =4 or SCCAI =2 ) at week 52 and no need for escalation of IBD therapy.

Clinical response after week 26 and week 52 (defined as ?3 in HBI or ?3 in SCCAI)

The proportion of patients with Fecal calprotectin <200 µg/g (<350 µg/g if Buhlman method is used) at week 26 and 52 .

Quality of life after 52 weeks using Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and short health scale (SHS).

The proportion of patients who reach therapeutics levels of E-6TGN levels (230-450 pmol/L) at week 6 and week 26.

Adverse events defined as any untoward or unfavourable medical occurrence in a human subject

Effects on intestinal permeability and microbiota

Timepoint(s) of evaluation of this end point: 6 weeks, 26 weeks, 52 weeks

Source(s) of Monetary Support

SOIBD

Umeå University

Västerbotten County Council