Post-Operative Crohn's Disease Outcome in Children (The POPCORN Trial): a Prospective Comparative Non-interventional Open Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Endoscopic recurrence (Rutgeerts score ≥ i2b)
研究概览
简要总结
Objectives: To examine the effect of prophylaxis therapy on clinical and endoscopic disease recurrence in children with Crohn's Disease (CD) following ileo-cecal resection. Hypothesis: Post-operative pediatric patients treated with anti-Tumor necrosis factor (TNF) prophylaxis will demonstrate lower endoscopic recurrence rates at 1 year and lower clinical recurrence rates at 2 years compared with thiopurines treated patients. Design: A multi-center, prospective, observational study. Patients with either thiopurines or anti-TNF prophylaxis will be enrolled 0-6 months following ileo-cecal resection. Prophylactic treatment will be decided at the discretion of the treating physician and not as a part of the study. According to standard-of-care, patients will undergo a colonoscopic evaluation 6-9 month following surgery. Study visits will be performed at 6 months following resection, 12 months, 18 months and 24 months. Setting: Porto group and IBD interest group pediatric gastroenterology centers. Participants: Children 6 year to 18 years (Overall, 84 patients) with CD following limited ileo-cecal resection. Main outcome measure: 1. Endoscopic recurrence at 1 year (according to Rutgeerts Score: i2-i4). 2. Clinical recurrence at 2 years (according to pediatric Crohn's disease activity index-PCDAI: ≥10). Secondary outcome measures: 1. Re-operation rate at 2 years. 2. Exacerbation-free quartiles at 2 years. 3. Anthropometric and laboratory measures including calprotectin at each visit. 4. Changes in fecal microbiome- baseline, 1 year and 2 years. Inclusion criteria: 1. CD with phenotypes L1 and L3 following ileo-cecal resection. 2. No active perianal disease. 3. Prophylactic therapy with either thiopurines or anti-TNF. Exclusion criteria: 1. Pregnancy. 2. Active perianal disease (draining fistula or abscess). 3. Post-operative intra-abdominal complication (fistula or abscess). Sample size: In order to demonstrate 20% difference in endoscopic recurrence rate between groups is significant, we will need to study 42 children in each group to be able to reject the null hypothesis that the failure rates between the groups are equal with probability (power) of 80% and a type I error probability of 0.05.
详细描述
Introduction Surgical intestinal resection of complicated or treatment refractory Crohn's disease (CD) is not uncommon. Ileocecal resection is the most frequent surgical intervention utilized in pediatric-onset CD, particularly in those with limited ileocecal disease. Only scarce data is available on the long-term outcome of patients following bowel resection in pediatric-onset CD . These studies have demonstrated that the risk for disease recurrence and additional surgical intervention is high in this population. Hence, as pediatric post-surgical patients are, by definition, high risk patients, prophylactic strategy is usually required. The most common prophylactic medications for post-operative recurrence are thiopurines and anti-TNF alpha agents. Adult randomized control trials assessing post-operative prophylaxis such as the PREVENT study and the POCER study have demonstrated similar short-term clinical recurrence rates (1 year) when comparing infliximab to placebo (PREVENT) or adalimumab to thiopurines (POCER). However, endoscopic recurrence rates did favor anti- tumor necrosis factor (TNF) prophylaxis. Apart from phenotypic characteristic and residual disease after resection there are data supporting fecal calprotectin as a strong predictor of disease recurrence. Both adult and pediatric guidelines recommend on performing a follow-up colonoscopy 6-9 month following surgical resection in-order to assess endoscopic activity by the Rutgeerts score and to adjust therapeutic regimens according to findings. Currently, there are no prospective or comparative studies assessing the effect of prophylactic post-operative therapies in children. Hence, it is the investigators aim is to assess the impact of postoperative prophylaxis on endoscopic and clinical recurrence in children with CD, following ileo-cecal resection using a prospective observational matched control design.
Hypothesis:
Post-operative pediatric patients treated with anti-TNF prophylaxis will demonstrate lower endoscopic recurrence rates at 1 year and lower clinical recurrence rates at 2 years compared with thiopurines treated patients.
Objectives:
Primary objective: To evaluate the effect of prophylactic therapy on clinical and endoscopic disease recurrence in children with CD following ileo-cecal resection.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Crohn's disease
- •Age: 6 - 17 years (inclusive)
- •L1 or L3 phenotypes
- •Ileocecal resection in the previous 3 months
- •No active perianal disease (including draining fistula or a peri-anal abscess)
- •Prophylactic therapy with either thiopurines or anti-TNF has been initiated
排除标准
- •Renal Failure
- •Current abscess or perforation of the bowel
- •Post-operative intra-abdominal complication (fistula or abscess)
- •Complicated or heavily draining perianal fistula (indolent non-draining or minimally draining fistula are not an exclusion criteria).
- •Previous malignancy
- •Sepsis or active bacterial infection
- •IBD unclassified
研究组 & 干预措施
Azathioprine or 6MP
Patients treated with thiopurines for post-operative prophylaxis.
干预措施: Azathioprine (Drug)
Anti-TNF drug
Patients treated with anti-TNF alpha monotherapy for post-operative prophylaxis.
干预措施: Anti-TNF Drug (Drug)
结局指标
主要结局
Endoscopic recurrence (Rutgeerts score ≥ i2b)
时间窗: 12 months following resection
According to Rutgeerts score The Rutgeerts score: i0-no lesions in the neoterminal ileum i1-fewer than 5 aphthous lesions in the neoterminal ileum i2a-lesions confined to the ileocolonic anastomosis, including anastomotic stenosis), i2b-more than 5 aphthous ulcers or larger lesions, with normal mucosa in between, in the neoterminal ileum, with or without anastomotic lesions i3-diffuse aphthous ileitis with diffusely inflamed mucosa i4-large ulcers with diffuse mucosal inflammation or nodules or stenosis in the neoterminal ileum.
次要结局
- Clinical recurrence according to PCDAI: ≥10(24 months)
- Re-operation rate(24 months)
- Exacerbation free quartiles(24 months)
研究者
Amit Assa
Head of IBD program
Schneider Children's Medical Center, Israel