Infliximab Top-down Study in Kids With Crohn's Disease
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 2
- 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 and azathioprine at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and azathioprine, 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 infliximab and azathioprine at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and azathioprine, in moderate-to-severe pediatric Crohn's disease (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; nQuery Advisor).
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 Intervention: Patients will be randomised to either top-down IFX treatment 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 azathioprine (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 oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, followed by tapering in 6 weeks until stop. Prednisolone 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) 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.
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: Azathioprine (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: Infliximab (Drug)
Step-up
Prednisolon and azathioprine; Patients will receive induction treatment with oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, then tapering of prednisolone in 6 weeks until stop, and receive oral azathioprine 2-3 mg/kg, once daily as maintenance treatment.
干预措施: Azathioprine (Drug)
Step-up
Prednisolon and azathioprine; Patients will receive induction treatment with oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, then tapering of prednisolone in 6 weeks until stop, and receive oral azathioprine 2-3 mg/kg, once daily as maintenance treatment.
干预措施: Prednisolon (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 Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 10 points
次要结局
- Mucosal healing(10 and 52 weeks)
- Adverse events rates(52 weeks)
- Adverse event rates(260 weeks)
- Long-term yearly clinical remission, response and mucosal healing (calprotectin) rates(260 weeks)
- Clinical response and remission rate(10 weeks)
- Therapy failure rates over time(52 weeks)
- Growth(10 and 52 weeks)
- Cumulative therapy use(260 weeks)
- Long-term yearly remission rates without need for additional CD related therapy or surgery(260 weeks)
- Yearly number of flares(260 weeks)
研究者
Lissy de Ridder
MD PhD, Pediatric gastroenterologist
Erasmus Medical Center