Low-dose Azathioprine and Allopurinol- Versus Azathioprine Monotherapy in Patients With Ulcerative Colitis: An Investigator-initiated, Open, Multicentre, Parallel-arm, Randomised Controlled Trial
试验速览
- 阶段
- 3 期
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Complete remission
研究概览
简要总结
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.
详细描述
Investigator initiated, multicentre, parallel arm, open, randomised controlled trial with blinded assessment
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Azathioprine and Allopurinol
干预措施: Azathioprine and Allopurinol (Drug)
Azathioprine
干预措施: Azathioprine (Drug)
结局指标
主要结局
Complete remission
时间窗: 52 weeks
Steroid- and biologic treatment free remission defined as total Mayo score ≤1 without rectal bleeding.
次要结局
- Time to remission(52 weeks)
- Clinical response(52 weeks)
- Endoscopic remission(52 weeks)
- Fecal calprotectin(52 weeks)
- Histological mucosal healing(52 weeks)
- Quality of life (SIBDQ)(52 weeks)
- Quality of life (SHS)(52 weeks)
- 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)
研究者
Sandra Bohn Thomsen
MD, Ph.D. candidate
Hvidovre University Hospital