A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Pragmatic Clinical Trial To Evaluate The Effectiveness Of Low Dose Oral Methotrexate In Patients With Pediatric Crohn's Disease Initiating Anti-TNF Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 306
- 试验地点
- 32
- 主要终点
- Percent of Participants Experiencing Treatment Failure
研究概览
简要总结
The purpose of this study is to determine whether adding low dose methotrexate to anti -TNF therapy is more effective than treatment with anti-TNF therapy alone in inducing and maintaining steroid-free remission for children with Crohn's Disease.
详细描述
Overall study duration: 6 years Multi-center study: up to 42 centers
Number of subjects: 425 Duration of treatment for each subject: up to 156 weeks (3 years)
The primary endpoint is percent of patients who experienced treatment failure over time.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- — 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric Crohn's Disease (PCD) patients, < 21 years of age, ≥20 kg, initiating anti-TNF therapy with infliximab or adalimumab (including biosimilars).
- •Diagnosis of Crohn's Disease (CD) established confirmed by the treating clinician, and established by standard clinical criteria (radiography, endoscopy, histology).
- •Ability to provide parental permission and child assent (where applicable), or adult consent for patients ages 18-20.
排除标准
- •Prior use of anti-TNF or other biological therapy for CD
- •Lack of stable home address that study medications can be mailed to
- •Anticipated short length of follow up at study center (plans for family to move, transition to adult GI (gastrointestinal) provider, etc.). Patients expected to leave practice < 12 months from enrollment should not be enrolled.
- •Concurrent pelvic or abdominal abscess. A recent history of abdominal or pelvic abscess, which is controlled, does not exclude the subject.
- •Prior intra-abdominal surgery without a clinically significant relapse (i.e. patients starting on anti-TNF for post-op prophylaxis or for endoscopic recurrence only should not be included)
- •Receipt of a live virus vaccine within the last 30 days
- •Pregnancy, planning to become pregnant, or high risk of pregnancy as determined by the local investigator
- •Breastfeeding
- •Refusal to stay abstinent or utilize 2 forms of birth control while on study medication (for female patients)
- •BMI > 98% for gender and age
- •Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years). A recent history of basal cell or squamous cell carcinoma, which is considered surgically cured, does not exclude the subject.Those with a recent history of colonic adenoma or dysplastic lesions should be excluded.
- •Known high alcohol consumption (more than seven drinks per week)
- •Patients with serum albumin < 2.5 g/dl
- •Patients with white blood cell count (WBC) < 3.0 x109th/L
- •Patients with platelet count < 100 x109th/L
- •Patients with initial elevation of liver enzymes (AST or ALT) > 1.5 times above normal limit
- •Patients with known active infection with Clostridium difficile (C. difficile) (untreated infection based on clinician assessment does not apply to colonization or infection controlled with current or prior treatment.)
- •Patients with pre-existing hepatic disease
- •Patients with pre-existing renal dysfunction (creatinine > 0.8 for children age<10, creatinine > 1.2 mg/dl for children age 10-18, and creatinine > 1.5 mg/dl for adults age 18 years and older).
- •Patients with a pre-existing chronic lung disease other than well controlled asthma
- •Current treatment with one of the following drugs: Probenecid (Probalan), Acitretin (Soriatane), Streptozocin (Zanosar), Azathioprine (Imuran, Azasan), 6-mercaptopurine (Purinethol, Purixan)
- •Other concerns about the patient/family's ability to participate in the study
研究组 & 干预措施
Methotrexate
Methotrexate (10, 12.5, or 15 mg), once weekly. Weight-based dosing. Ondansetron (4 mg), twice weekly, 1 hour prior to methotrexate dose and the morning after methotrexate dose.
Folic Acid (1 mg) daily
干预措施: Methotrexate (Drug)
Sugar pill (placebo)
Placebo for methotrexate, once weekly. Placebo for ondansetron, twice weekly, 1 hour prior to methotrexate placebo dose and the morning after methotrexate placebo dose.
Folic Acid (1 mg) daily
干预措施: Sugar pill (placebo) (Other)
结局指标
主要结局
Percent of Participants Experiencing Treatment Failure
时间窗: From randomization until treatment failure, assessed up to 3 years.
Treatment failure is defined as follows: 1. Failure to achieve remission (short pediatric Crohn's disease activity index \[SPCDAI\] \< 15) by the week 26 visit; 2. If study initiated on steroids, failure to complete steroid taper by week 16; 3. Short pediatric Crohn's disease activity index (SPCDAI) ≥ 15 attributed to active Crohn's disease, at two or more consecutive visits beyond the week 26 visit. Elevated SPCDAI (≥ 15) due to a non-Inflammatory Bowel Disease (IBD) reason does not count toward this outcome; 4. Hospitalization for active Inflammatory Bowel Disease or abdominal surgery after week 25; 5. Use of oral prednisone or prednisolone, enteral release budesonide, or intravenous (IV) methylprednisolone for over 10 weeks cumulatively, beyond week 16; 6. Discontinuation of anti-TNF agent and/or study drug for lack of effectiveness or toxicity.
次要结局
- Mean Patient Reported Outcome Measurement and Information System (PROMIS ) Pain Interference T-score-52 Weeks(Weeks 52 from randomization)
- Mean Patient Reported Outcome Measurement and Information System (PROMIS ) Pain Interference T-score-week 104(104 weeks from randomization)
- Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T Score-week 52(Week 52 from randomization)
- Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T Score-week 104(104 weeks from randomization)
- Percent of Patients With Positive Anti-TNF Antibody(Between 6 months and 2 years from randomization)