Beneficial and Harmful Effects of Azathioprine and Allopurinol Versus Standard Azathioprine Therapy for Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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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
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Investigator initiated, multicentre, parallel arm, open, randomised controlled trial with blinded assessment

Official Title
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Low-dose Azathioprine and Allopurinol- Versus Azathioprine Monotherapy in Patients With Ulcerative Colitis: An Investigator-initiated, Open, Multicentre, Parallel-arm, Randomised Controlled Trial

Conditions
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Colitis, Ulcerative, Colitis Ulcerative Exacerbation

Intervention / Treatment
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* Drug: Azathioprine and Allopurinol
* Drug: Azathioprine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azathioprine and Allopurinol<br> | Drug: Azathioprine and Allopurinol<br>* Low dose Azathioprine in combination with allopurinol 100 mg for 1 year<br>|
| Active Comparator: Azathioprine<br> | Drug: Azathioprine<br>* Standard weight based azathioprine dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission | Steroid- and biologic treatment free remission defined as total Mayo score ≤1 without rectal bleeding. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to remission |  | 52 weeks | 
| Clinical response | defined as a Mayo score between ≤1 to < 3 | 52 weeks | 
| Endoscopic remission | defined as a Mayo subscore of 0 | 52 weeks | 
| Fecal calprotectin |  | 52 weeks | 
| Histological mucosal healing |  | 52 weeks | 
| Quality of life (SIBDQ) | Using Inflammatory Bowel Disease Questionnaire Quality of life (SIBDQ) | 52 weeks | 
| Quality of life (SHS) | Using the Short health scale (SHS) | 52 weeks | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Azathioprine, Allopurinol, Antimetabolites, Ulcerative Colitis