Colitis, Ulcerative, Colitis Ulcerative Exacerbation
Conditions
Keywords
Azathioprine, Allopurinol, Antimetabolites, Ulcerative Colitis
Brief summary
Azathioprine is considered first line immunomodulatory therapy for patients with ulcerative colitis. Up to 50% are treatment failures or experience adverse events leading to treatment withdrawal. Recent evidence suggests that the combination of allopurinol and low dose azathioprine increases the proportion of treatment responders and reduce the risk of adverse events. Objectives: To evaluate the beneficial and harmful effects of low dose azathioprine and allopurinol versus standard azathioprine monotherapy in patients with ulcerative colitis.
Detailed description
Investigator initiated, multicentre, parallel arm, open, randomised controlled trial with blinded assessment
Interventions
DRUGAzathioprine and Allopurinol
Low dose Azathioprine in combination with allopurinol 100 mg for 1 year
DRUGAzathioprine
Standard weight based azathioprine dosage
Sponsors
Aalborg University Hospital
Zealand University Hospital
University of Copenhagen
Odense University Hospital
Aarhus University Hospital
Viborg Regional Hospital
Vejle Hospital
Sydvestjysk Hospital Esbjerg
Hvidovre University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Willingness to comply with all trial procedures and being available for the duration of the trial. * Clinically and histologically verified ulcerative colitis eligible for treatment with thiopurines due to steroid dependence (failure to taper steroid or starting a second course of systemic steroids within 1 year) or patients with the need for rescue therapy with anti-TumorNecrosisFactorα (anti-TNFα) * A sigmoidoscopy or colonoscopy showing active inflammation during the present disease flare * Negative stool test for pathogen bacteria incl. Clostridium difficile * Informed consent. * Normal TPMT genotype (homozygous wild-type). * Oral 5-Asa dose stable for 2 weeks
Exclusion criteria
* Kidney disease with a GlomerularFiltration Rate (GFR) \< 50 ml/min. * Persistent alanine aminotransferase U/L (ALT) twice above upper limit of the normal range. * Participation in other interventional clinical trials. * Pregnancy or breastfeeding. * Previous thiopurin treatment. * Previous or current treatment with other biologics than anti-TNFα * Not being able to comply with the study, assessed by investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission | 52 weeks | Steroid- and biologic treatment free remission defined as total Mayo score ≤1 without rectal bleeding. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to remission | 52 weeks | — |
| Clinical response | 52 weeks | defined as a Mayo score between ≤1 to \< 3 |
| Endoscopic remission | 52 weeks | defined as a Mayo subscore of 0 |
| Fecal calprotectin | 52 weeks | — |
| Histological mucosal healing | 52 weeks | — |
| Quality of life (SIBDQ) | 52 weeks | Using Inflammatory Bowel Disease Questionnaire Quality of life (SIBDQ) |
| Quality of life (SHS) | 52 weeks | Using the Short health scale (SHS) |
| Correlation between 6ThioGuanineNucleotiude (6TGN) and clinical mayo score | From week 6 to week 52 | — |
| Correlation between 6TGN and standard blood tests | From week 6 to week 52 | — |
| Correlation between 6TGN and fecal calprotectin | From week 6 to week 52 | — |
| Correlation between 6TGN endoscopic mayo score | From week 6 to week 52 | — |
| Correlation between 6TGN and histological mucosal healing | From week 6 to week 52 | — |
| Adverse events | 52 weeks | — |
Countries
Denmark
Outcome results
None listed