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

Primary Purpose

Colitis, Ulcerative, Colitis Ulcerative Exacerbation

Status
Unknown status
Phase
Phase 3
Locations
Denmark
Study Type
Interventional
Intervention
Azathioprine and Allopurinol
Azathioprine
Sponsored by
Hvidovre University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colitis, Ulcerative focused on measuring Azathioprine, Allopurinol, Antimetabolites, Ulcerative Colitis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hvidovre university hospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Azathioprine and Allopurinol

Azathioprine

Arm Description

Outcomes

Primary Outcome Measures

Complete remission
Steroid- and biologic treatment free remission defined as total Mayo score ≤1 without rectal bleeding.

Secondary Outcome Measures

Time to remission
Clinical response
defined as a Mayo score between ≤1 to < 3
Endoscopic remission
defined as a Mayo subscore of 0
Fecal calprotectin
Histological mucosal healing
Quality of life (SIBDQ)
Using Inflammatory Bowel Disease Questionnaire Quality of life (SIBDQ)
Quality of life (SHS)
Using the Short health scale (SHS)
Correlation between 6ThioGuanineNucleotiude (6TGN) and clinical mayo score
Correlation between 6TGN and standard blood tests
Correlation between 6TGN and fecal calprotectin
Correlation between 6TGN endoscopic mayo score
Correlation between 6TGN and histological mucosal healing
Adverse events

Full Information

First Posted
January 27, 2017
Last Updated
August 14, 2018
Sponsor
Hvidovre University Hospital
Collaborators
Aalborg University Hospital, Zealand University Hospital, University of Copenhagen, Odense University Hospital, Aarhus University Hospital, Viborg Regional Hospital, Vejle Hospital, Sydvestjysk Hospital Esbjerg
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1. Study Identification

Unique Protocol Identification Number
NCT03101800
Brief Title
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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
December 14, 2016 (Actual)
Primary Completion Date
November 14, 2019 (Anticipated)
Study Completion Date
December 14, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hvidovre University Hospital
Collaborators
Aalborg University Hospital, Zealand University Hospital, University of Copenhagen, Odense University Hospital, Aarhus University Hospital, Viborg Regional Hospital, Vejle Hospital, Sydvestjysk Hospital Esbjerg

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colitis, Ulcerative, Colitis Ulcerative Exacerbation
Keywords
Azathioprine, Allopurinol, Antimetabolites, Ulcerative Colitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Azathioprine and Allopurinol
Arm Type
Experimental
Arm Title
Azathioprine
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Azathioprine and Allopurinol
Intervention Description
Low dose Azathioprine in combination with allopurinol 100 mg for 1 year
Intervention Type
Drug
Intervention Name(s)
Azathioprine
Intervention Description
Standard weight based azathioprine dosage
Primary Outcome Measure Information:
Title
Complete remission
Description
Steroid- and biologic treatment free remission defined as total Mayo score ≤1 without rectal bleeding.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Time to remission
Time Frame
52 weeks
Title
Clinical response
Description
defined as a Mayo score between ≤1 to < 3
Time Frame
52 weeks
Title
Endoscopic remission
Description
defined as a Mayo subscore of 0
Time Frame
52 weeks
Title
Fecal calprotectin
Time Frame
52 weeks
Title
Histological mucosal healing
Time Frame
52 weeks
Title
Quality of life (SIBDQ)
Description
Using Inflammatory Bowel Disease Questionnaire Quality of life (SIBDQ)
Time Frame
52 weeks
Title
Quality of life (SHS)
Description
Using the Short health scale (SHS)
Time Frame
52 weeks
Title
Correlation between 6ThioGuanineNucleotiude (6TGN) and clinical mayo score
Time Frame
From week 6 to week 52
Title
Correlation between 6TGN and standard blood tests
Time Frame
From week 6 to week 52
Title
Correlation between 6TGN and fecal calprotectin
Time Frame
From week 6 to week 52
Title
Correlation between 6TGN endoscopic mayo score
Time Frame
From week 6 to week 52
Title
Correlation between 6TGN and histological mucosal healing
Time Frame
From week 6 to week 52
Title
Adverse events
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Hvidovre university hospital
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra B Thomsen
Phone
+4538626540
Email
sandra.bohn.thomsen@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35274092
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.
Results Reference
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Beneficial and Harmful Effects of Azathioprine and Allopurinol Versus Standard Azathioprine Therapy for Patients With Ulcerative Colitis

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