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

Colitis, Ulcerative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03101800
• Other study ID #: AAUC Study
• Status: Recruiting
• Phase: Phase 3
• Start date: December 14, 2016
• Est. completion date: December 14, 2019

Study information

• Verified date: August 2018
• Source: Hvidovre University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Investigator initiated, multicentre, parallel arm, open, randomised controlled trial with blinded assessment

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: December 14, 2019
• Est. primary completion date: November 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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-TumorNecrosisFactora (anti-TNFa)

• 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-TNFa

• Not being able to comply with the study, assessed by investigator

Related Conditions & MeSH terms

• Colitis
• Colitis Ulcerative Exacerbation
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Azathioprine and Allopurinol
Low dose Azathioprine in combination with allopurinol 100 mg for 1 year
• Azathioprine
Standard weight based azathioprine dosage

Locations

Country	Name	City	State
Denmark	Hvidovre university hospital	Hvidovre

Sponsors (9)

Lead Sponsor	Collaborator
Hvidovre University Hospital	Aalborg Universitetshospital, Aarhus University Hospital, Odense University Hospital, Regional Hospital Viborg, Sydvestjysk Hospital Esbjerg, University of Copenhagen, Vejle Hospital, Zealand University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission	Steroid- and biologic treatment free remission defined as total Mayo score =1 without rectal bleeding.	52 weeks
Secondary	Time to remission		52 weeks
Secondary	Clinical response	defined as a Mayo score between =1 to < 3	52 weeks
Secondary	Endoscopic remission	defined as a Mayo subscore of 0	52 weeks
Secondary	Fecal calprotectin		52 weeks
Secondary	Histological mucosal healing		52 weeks
Secondary	Quality of life (SIBDQ)	Using Inflammatory Bowel Disease Questionnaire Quality of life (SIBDQ)	52 weeks
Secondary	Quality of life (SHS)	Using the Short health scale (SHS)	52 weeks
Secondary	Correlation between 6ThioGuanineNucleotiude (6TGN) and clinical mayo score		From week 6 to week 52
Secondary	Correlation between 6TGN and standard blood tests		From week 6 to week 52
Secondary	Correlation between 6TGN and fecal calprotectin		From week 6 to week 52
Secondary	Correlation between 6TGN endoscopic mayo score		From week 6 to week 52
Secondary	Correlation between 6TGN and histological mucosal healing		From week 6 to week 52
Secondary	Adverse events		52 weeks