Clinical trial NCT03101800: Beneficial and Harmful Effects of Azathioprine and Allopurinol Versus Standard Azathioprine Therapy for Patients With Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Colitis, Ulcerative
Colitis Ulcerative Exacerbation
Keywords: Azathioprine
Allopurinol
Antimetabolites
Ulcerative Colitis
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: Aalborg University Hospital
name: Zealand University Hospital
name: University of Copenhagen
name: Odense University Hospital
name: Aarhus University Hospital
name: Viborg Regional Hospital
name: Vejle Hospital
name: Sydvestjysk Hospital Esbjerg
First posted: 2017-04-05
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Complete remission
timeFrame: 52 weeks
Secondary outcomes:
measure: Time to remission
timeFrame: 52 weeks
measure: Clinical response
timeFrame: 52 weeks
measure: Endoscopic remission
timeFrame: 52 weeks
measure: Fecal calprotectin
timeFrame: 52 weeks
measure: Histological mucosal healing
timeFrame: 52 weeks
measure: Quality of life (SIBDQ)
timeFrame: 52 weeks
measure: Quality of life (SHS)
timeFrame: 52 weeks
measure: Correlation between 6ThioGuanineNucleotiude (6TGN) and clinical mayo score
timeFrame: From week 6 to week 52
measure: Correlation between 6TGN and standard blood tests
timeFrame: From week 6 to week 52
measure: Correlation between 6TGN and fecal calprotectin
timeFrame: From week 6 to week 52
measure: Correlation between 6TGN endoscopic mayo score
timeFrame: From week 6 to week 52
measure: Correlation between 6TGN and histological mucosal healing
timeFrame: From week 6 to week 52
measure: Adverse events
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre university hospital
Study officials:
References:
citation: Kiszka-Kanowitz M, Theede K, Thomsen SB, Bjerrum JT, Brynskov J, Gottschalck IB, Akimenko E, Hilsted KL, Neumann A, Wildt S, Larsen L, Munk JK, Ibsen PH, Janjua HGR, Gluud LL, Mertz-Nielsen A. Low-dose azathioprine and allopurinol versus azathioprine monotherapy in patients with ulcerative colitis (AAUC): An investigator-initiated, open, multicenter, parallel-arm, randomised controlled trial. EClinicalMedicine. 2022 Mar 5;45:101332. doi: 10.1016/j.eclinm.2022.101332. eCollection 2022 Mar.