Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence: Systematic Versus Endoscopic-directed Treatment. A Multi-center, Randomized, Clinical Practice Evaluation Study.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 63
- 试验地点
- 4
- 主要终点
- Endoscopic remission
研究概览
简要总结
The objective of this study is to evaluate if in the prevention of postoperative recurrence of ileal Crohn's disease immediate initiation of azathioprine postoperatively is superior to delayed (6- 12 mths.) introduction of azathioprine upon disease recurrence assessed by endoscopic criteria. The primary endpoint, disease recurrence, encompasses symptomatic and surgical recurrence as well as severe endoscopic lesions at the final, 2 year, assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Scheduled surgery for Crohn's disease (CD) with ileocolonic resection. Diagnosis of CD confirmed at least 4 months prior to surgery based on radiology and/or endoscopy.
- •Having an increased risk for postoperative relapse for any of the following reasons: (1) active inflammatory disease with C-reactive protein level (CRP) elevated above 10 mg/L, or the use of antibiotics, steroids or biological therapy including infliximab for active ileal disease within 2 months before surgery which were administered for Crohn's disease and not for another unrelated intercurrent inflammatory or infectious disease; (2) perforating disease defined as the presence of entero-enteric or enterocutaneous fistulas or perivisceral abscess formation within 2 months before surgery. Perianal fistulizing disease will not be considered as an indication of perforating disease in the ileum or right-sided colon. (3) Previous ileo-colonic resection, (4) active smoking, (5) age below
- •Males and females 16-75 years old.
- •Curative surgical resection. All macroscopically inflamed colonic segments (except for anorectal involvement) are to be removed at surgery. Stricturoplasties in small bowel segments not involving the anastomotic region are allowed.
- •Patients able to start oral nutrition and oral therapy within 14 days from surgery.
- •Patients able and willing to give written informed consent
- •Women of childbearing potential should have a negative pregnancy test at inclusion.
排除标准
- •Patients who only had strictureplasties or ileal/colonic resection without a new ileo-colonic anastomosis. Patients with ileorectal anastomosis.
- •Patients with no increased risk of postoperative relapse as defined before.
- •Patients with a known intolerance to azathioprine/6-mercaptopurine or with known homozygous thiopurine methyltransferase-low mutation.
- •Patients in whom more than 100 cm of small bowel has been previously resected.
- •Patients with active perianal disease or colorectal stenosis precluding ileocolonoscopy
- •Patients with sepsis or other postoperative complications necessitating use of antibiotics for more than 14 days after surgery.
- •Patients with liver test abnormalities (serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, bilirubin > 2 ULN), leucopenia (<3000 white blood cell count /µL, <1500 neutrophils /µL), thrombopenia with < 50.000 platelets/mm
- •Patients with severe renal, pulmonary or cardiac disease.
- •Pregnant or lactating women.
- •Ongoing alcohol or substance abuse.
- •Ongoing or recent (within 6 months) infectious disease (viral hepatitis, tuberculosis, AIDS, Herpes zoster related disease).
- •Known malignancy 5 years from surgery except for superficial epithelioma of the skin with curative resection.
研究组 & 干预措施
Systematic azathioprine group
Patients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks.
干预措施: Azathioprine (Drug)
Systematic azathioprine group
Patients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks.
干预措施: Ileocolonoscopy (Procedure)
Systematic azathioprine group
Patients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks.
干预措施: Small bowel follow trough (Procedure)
Endoscopy-driven azathioprine group
Patients randomized to the endoscopy-driven azathioprine group received no Crohn's disease specific treatment for 26 weeks postoperatively. A first ileocolonoscopy was performed at week 26. In case of endoscopic recurrence (Rutgeerts' score i2 or higher), azathioprine was introduced at a dose of 2.0-2.5 mg/kg until week 102. If not, an ileocolonoscopy was repeated at week 52, and azathioprine started in case of endoscopic recurrence. If no endoscopic recurrence was observed, no Crohn's disease-specific treatment was given until week 102.
干预措施: Azathioprine in case of endoscopic recurrence (Drug)
Endoscopy-driven azathioprine group
Patients randomized to the endoscopy-driven azathioprine group received no Crohn's disease specific treatment for 26 weeks postoperatively. A first ileocolonoscopy was performed at week 26. In case of endoscopic recurrence (Rutgeerts' score i2 or higher), azathioprine was introduced at a dose of 2.0-2.5 mg/kg until week 102. If not, an ileocolonoscopy was repeated at week 52, and azathioprine started in case of endoscopic recurrence. If no endoscopic recurrence was observed, no Crohn's disease-specific treatment was given until week 102.
干预措施: Ileocolonoscopy (Procedure)
Endoscopy-driven azathioprine group
Patients randomized to the endoscopy-driven azathioprine group received no Crohn's disease specific treatment for 26 weeks postoperatively. A first ileocolonoscopy was performed at week 26. In case of endoscopic recurrence (Rutgeerts' score i2 or higher), azathioprine was introduced at a dose of 2.0-2.5 mg/kg until week 102. If not, an ileocolonoscopy was repeated at week 52, and azathioprine started in case of endoscopic recurrence. If no endoscopic recurrence was observed, no Crohn's disease-specific treatment was given until week 102.
干预措施: Small bowel follow trough (Procedure)
结局指标
主要结局
Endoscopic remission
时间窗: Week 102
The proportion of patients with endoscopic remission (Rutgeerts' postoperative endoscopic score i0 or i1) at 102 weeks
次要结局
- Complete endoscopic remission(Week 102)
- Absence of endoscopic relapse(Week 102)
- Clinical remission(Week 102)
- Sustained clinical remission(Week 102)
- Radiological remission(Week 102)