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

Phase 3

• Conditions: Colitis, Ulcerative; Colitis Ulcerative Exacerbation
• Interventions: Drug: Azathioprine and Allopurinol; Drug: Azathioprine

• Registration Number: NCT03101800
• Lead Sponsor: Hvidovre University Hospital

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

Study Timeline

• Study Start: 2016-12-14
• Study First Submitted: 2017-01-27
• Study First Submitted QC: 2017-03-29
• Study First Posted: 2017-04-05
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-14
• Last Update Posted: 2018-08-15
• Primary Completion: 2019-11-14
• Study Completion: 2019-12-14

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 84

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azathioprine and Allopurinol	Azathioprine and Allopurinol	-
Azathioprine	Azathioprine	-

Primary Outcome Measures

Name	Time	Method
Complete remission	52 weeks	Steroid- and biologic treatment free remission defined as total Mayo score ≤1 without rectal bleeding.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Hvidovre university hospital; 🇩🇰 Hvidovre, Denmark