Top-down Infliximab Study in Kids With Crohn's Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 13
- 主要终点
- Clinical remission without need for additional CD related therapy or surgery
研究概览
简要总结
The purpose of this study is to determine whether a top-down treatment approach, prescribing infliximab (IFX) and azathioprine (AZA) at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and AZA or exclusive enteral nutrition (EEN) and AZA, in moderate-to-severe pediatric Crohn's disease (CD) patients.
详细描述
Objective: The purpose of this study is to determine whether a top-down treatment approach, prescribing IFX and AZA at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and AZA or EEN and AZA, in moderate-to-severe pediatric CD patients.
Sample size: We will include 100 (2 x 50) patients. With these numbers a difference of 60% and 85% (= 25) can be shown at a power of 80% (2-sided α 0.05).
Study design: an international open-label randomised controlled trial Study population: Children (age 3-17 yrs) with new-onset, untreated, CD with moderate-to-severe disease activity (weighted Pediatric CD Index [wPCDAI] >40) Intervention: Patients will be randomised to either top-down or conventional step-up treatment.
Treatment arm 1: Top-down IFX treatment will consist of a total of 5 IFX infusions of 5 mg/kg (IFX induction at week 0, 2 and 6, followed by 2 maintenance infusions every 8 weeks) combined with oral AZA 2-3 mg/kg once daily. AZA therapy will continue after the last IFX infusion to maintain remission.
Treatment arm 2: Step-up treatment will consist of standard induction treatment by either oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, followed by tapering in 6 weeks until stop, or EEN with polymeric feeding for 6-8 weeks after which normal foods are gradually reintroduced within 2-3 weeks. Either of these induction treatments will be combined with oral AZA 2-3 mg, once daily, as maintenance treatment.
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
- None
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children (age 3-17 years, both male and female, weight >10kg) with new-onset,
- •untreated CD with moderate-to-severe disease activity assessed by a wPCDAI >40 will be eligible for inclusion after a diagnosis of CD was made based on the Porto criteria
排除标准
- •Patients with the following characteristics will be excluded:
- •immediate need for surgery,
- •symptomatic stenosis or stricture in the bowel due to scarring,
- •active perianal fistulas,
- •severe co-morbidity,
- •severe infection such as sepsis or opportunistic infections,
- •positive stool culture,
- •positive Clostridium difficile assay,
- •positive tuberculin test or a chest radiograph consistent with tuberculosis or malignancy,
- •those already started with CD specific therapy,
- •patients with a suspected or
- •definitive pregnancy
研究组 & 干预措施
Top-down
Infliximab and azathioprine; patients will receive 5 infliximab infusions of 5 mg/kg (IFX induction at week 0, 2 and 6, followed by 2 maintenance infusions every 8 weeks). IFX will be discontinued after 5 IFX infusions. Patients will also receive oral azathioprine 2-3 mg/kg, once daily as maintenance treatment.
干预措施: Infliximab (Drug)
Top-down
Infliximab and azathioprine; patients will receive 5 infliximab infusions of 5 mg/kg (IFX induction at week 0, 2 and 6, followed by 2 maintenance infusions every 8 weeks). IFX will be discontinued after 5 IFX infusions. Patients will also receive oral azathioprine 2-3 mg/kg, once daily as maintenance treatment.
干预措施: Azathioprine (Drug)
Step-up
Step-up treatment will consist of standard induction treatment by either oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, followed by tapering in 6 weeks until stop, or EEN with polymeric feeding for 6-8 weeks after which normal foods are gradually reintroduced within 2-3 weeks. Either of these induction treatments will be combined with oral AZA 2-3 mg, once daily, as maintenance treatment.
干预措施: Prednisolone (Drug)
Step-up
Step-up treatment will consist of standard induction treatment by either oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, followed by tapering in 6 weeks until stop, or EEN with polymeric feeding for 6-8 weeks after which normal foods are gradually reintroduced within 2-3 weeks. Either of these induction treatments will be combined with oral AZA 2-3 mg, once daily, as maintenance treatment.
干预措施: Exclusive enteral nutrition (Other)
Step-up
Step-up treatment will consist of standard induction treatment by either oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, followed by tapering in 6 weeks until stop, or EEN with polymeric feeding for 6-8 weeks after which normal foods are gradually reintroduced within 2-3 weeks. Either of these induction treatments will be combined with oral AZA 2-3 mg, once daily, as maintenance treatment.
干预措施: Azathioprine (Drug)
结局指标
主要结局
Clinical remission without need for additional CD related therapy or surgery
时间窗: 52 weeks
Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points
次要结局
- Change in height Z-scores(10 and 52 weeks)
- Change bone age(10 and 52 weeks)
- Therapy failure rates over time(52 weeks)
- Cumulative therapy use(52 weeks, and 260 weeks)
- Long-term yearly number of flares(260 weeks)
- Clinical remission rates(10 and 52 weeks)
- Clinical response rates(10 weeks)
- Change in BMI Z-scores(10 and 52 weeks)
- Long-term yearly remission rates without need for additional CD related therapy or surgery(260 weeks)
- Long-term yearly clinical remission rates(260 weeks)
- Mucosal healing(10 and 52 weeks)
- Change in Tanner stage(10 and 52 weeks)
- Adverse events rates(52 weeks, and 260 weeks)
- Long-term yearly mucosal healing (calprotectin) rates(260 weeks)
研究者
Lissy de Ridder
Pediatric Gastroenterologist
Erasmus Medical Center