Efficacy of Optimized Thiopurine Therapy in Ulcerative Colitis (OPTIC)
试验速览
- 阶段
- 3 期
- 入组人数
- 136
- 试验地点
- 12
- 主要终点
- Clinical and endoscopic remission
研究概览
简要总结
This project is a double-blind, randomized, placebo-controlled, multicenter trial in the Netherlands. The aim of this study is to investigate the therapeutic efficacy of optimized 6-mercaptopurine (6-MP) in ulcerative colitis patients. Therapeutic drug monitoring (TDM) will be performed in order to optimize treatment outcomes and objective endoscopic endpoints will be used.
详细描述
Subjects will receive treatment with oral prednisone 40 mg/day for 2 weeks, followed by fixed tapering over 6 weeks. Half of the subjects will be randomized to concomitant 6-MP 1-1.5 mg/kg/day and half will receive concomitant placebo treatment. During the entire course of the trial all subjects will receive maintenance treatment with 5-ASA in an oral dose of at least 2 gram per day. Subjects will be subjected to one colonoscopy at baseline and one sigmoidoscopy in week 52 in order to assess endoscopic disease activity.
Data will be collected using electronic case report forms (eCRF) with Castor EDC. Quality and data validation procedures will be applied to ensure the validity and accuracy of the clinical database. Monitoring of the study will be done according to the GCP guidelines and following a monitoring plan. The financier of the study, ZonMw Goed Gebruik Geneesmiddelen, has the right to perform an audit if seen necessary.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of UC by endoscopy and histopathology
- •Patients between 18 and 80 years of age
- •Active disease, despite oral treatment with at least 2g/day 5-ASA
- •Treatment with oral corticosteroids is required
排除标准
- •Prior treatment with thiopurines
- •Prior treatment with biologics (e.g. anti-TNF agents and vedolizumab)
- •Current pregnancy (a pregnancy test will be performed if necessary according to the treating physician)
- •Chronic Obstructive Pulmonary Disease (COPD)
- •Acute coronary heart disease
- •(Bacterial) gastroenteritis has to be treated first
- •Coagulation disorders
- •Active malignancy
- •History of colonic dysplasia/cancer
- •Extensive colonic resection, i.e. subtotal colectomy with <15 cm colon in situ
- •Concomitant therapy with drugs interfering with MP metabolism, like allopurinol, ribavirin or anti-epileptics.
- •Known systemic fungal infections or parasitic infections have to be treated first
- •Known duodenal or ventricular ulcus
- •Substance abuse, such as alcohol (> 80 gram/day - one standard glass contains 10 gram of alcohol), I.V. drugs and inhaled drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years. Subjects receiving methadone within the past 2 years are also excluded
- •Positive tuberculosis screen (when a screening is performed at the discretion of the treating physician)
- •Active hepatitis B virus or hepatitis C virus infection defined as a positive anti-HCV, HBsAg and/or anti-HBcore screening.
- •Leucopenia (Neutrophil count < 1,8x10^9/L)
- •Thrombopenia (Platelets < 90x10^9/L)
- •Elevated liver enzymes (>2x ULN)
- •Abnormal renal function (eGFR< 30 mL/min)
- •Other conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedure
研究组 & 干预措施
Mercaptopurine (Purinethol)
Mercaptopurine (Purinethol),1-1.5 mg/kg/day oral, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.
干预措施: Mercaptopurine (Purinethol) (Drug)
Mercaptopurine (Purinethol)
Mercaptopurine (Purinethol),1-1.5 mg/kg/day oral, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.
干预措施: Mesalamine (Drug)
Mercaptopurine (Purinethol)
Mercaptopurine (Purinethol),1-1.5 mg/kg/day oral, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.
干预措施: Prednisone (Drug)
Placebo
Placebo, 1-1.5 mg/kg/day, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.
干预措施: Placebo (Drug)
Placebo
Placebo, 1-1.5 mg/kg/day, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.
干预措施: Mesalamine (Drug)
Placebo
Placebo, 1-1.5 mg/kg/day, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.
干预措施: Prednisone (Drug)
结局指标
主要结局
Clinical and endoscopic remission
时间窗: After 52 weeks of treatment
Defined as a SCCAI-score ≤ 4, a UCEIS-score ≤ 3 and a total Mayo score ≤ 2, with no individual subscore \>1.
次要结局
- 6-MMP levels(Every 6-12 weeks during 52 weeks of treatment)
- Occurrence of treatment failure(Continue during 52 weeks of treatment)
- Occurrence of upscaling treatment(Continue during 52 weeks of treatment)
- Occurrence of subjective thiopurine intolerance(Every 6-12 weeks during 52 weeks of treatment)
- (Serious) Adverse Events(Continue during 52 weeks of treatment)
- Treatment costs(Every 3 months during 52 weeks of treatment)
- Leukocyte counts(Every 6 weeks during 52 weeks of treatment)
- 6-TGN levels(Every 6-12 weeks during 52 weeks of treatment)
- Liver function tests(Every 6-12 weeks during 52 weeks of treatment)
研究者
M. Lowenberg
Gastroenterologist
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)