Effect of azathioprine and allopurinol compared to azaothioprine monotherapy in ulcerative colitis

• Register: EUCTR
• Last refreshed on: 12 October 2021
• Main ID: EUCTR2016-002433-30-DK
• Date of registration: 21/06/2016
• Prospective Registration: Yes
• Primary sponsor: Hvidovre Hospital
• Public title: Effect of azathioprine and allopurinol compared to azaothioprine monotherapy in ulcerative colitis
• Scientific title: Low-dose azathioprine and allopurinol versus azathioprine monotherapy for patients with ulcerative colitis: protocol for an investigator initiated, open, multicentre, parallel arm, randomised controlled trial - AAUC
• Date of first enrolment: 25/08/2016
• Target sample size: 84
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002433-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Multicentre; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Denmark

Contacts

• Name: Anette Mertz Nielsen
• Affiliation: Hvidovre Hospital

• Name: Anette Mertz Nielsen
• Affiliation: Hvidovre Hospital

Key inclusion & exclusion criteria

Inclusion criteria:
• Age 18 - 80 years at the time of inclusion
• Willing to comply with all trial procedures and 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-TNFa.
• A sigmoidoscopy showing active inflammation in the present disease flare
• Negative stool test for pathogen bacteria incl. C. difficile
• Willing to give informed consent;
• Normal TPMT genotype. TPMT can be measured as genotype or phenotype. A normal TPMT genotype is ‘wild type’. A normal TPMT phenotype is > 14 U/ml ery
• Oral 5-ASA dose stable for two weeks

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion criteria:
• Kidney disease with a GRF < 50.
• Persistent alanine aminotransferase (ALT) twice above upper limit of the normal range;
• Infectious diarrhoea.
• Participation in other interventional clinical trials.
• Pregnancy or breastfeeding
• Previous or current treatment with other biologics than anti-TNFa
• Not being able to comply with the study, assessed by investigator


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: Imurel
Pharmaceutical Form: Tablet
INN or Proposed INN: Azathioprine
CAS Number: 446-86-6
Other descriptive name: AZATHIOPRINE
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 25-50

Trade Name: Allopurinol
Pharmaceutical Form: Tablet
INN or Proposed INN: ALLOPURINOL
CAS Number: 315-30-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): Steroid and biologic treatment free remission defined as total Mayo score =1without rectal bleeding

Main Objective: To evaluate the beneficial and harmful effects of low dose azathioprine and allopurinol versus standard azathioprine monotherapy for patients with ulcerative colitis

Timepoint(s) of evaluation of this end point: at 52 weeks

Secondary Objective: • Time to remission (defined as described above)
• Clinical response after 52 weeks (defined as a Mayo score between =1 to < 3)
• Endoscopic remission after 52 weeks (defined as a Mayo subscore of 0)
• Fecal calprotectin levels after 52 weeks.
• Quality of life after 26 and 52 weeks using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and short health scale (SHS).
• Correlation between E-6TGN and clinical, laboratory, endoscopic and histological indices.
• Histological mucosal healing after 52 weeks.
• Adverse events

Secondary Outcome(s)

Secondary end point(s): • Time to remission (defined as described above)
• Clinical response after 52 weeks (defined as a Mayo score between =1 to < 3)
• Endoscopic remission after 52 weeks (defined as a Mayo subscore of 0)
• Fecal calprotectin levels after 52 weeks.
• Quality of life after 26 and 52 weeks. We will assess the quality of life using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and short health scale (SHS)
• Histological mucosal healing after 52 weeks.
• Correlation between E-6TGN and clinical, laboratory, endoscopic and histological indices after 52 weeks
• Adverse events

Timepoint(s) of evaluation of this end point: At week 52

Secondary ID(s)

AAUC.01.02

Source(s) of Monetary Support

Regionernes medicinpulje

Ethics review

Status: Approved
Approval date: 25/08/2016
Contact: