Predicting Relapse of Ulcerative Colitis With Gastrointestinal Ultrasound
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Endoscopic relapse
研究概览
简要总结
Rationale:
Ulcerative colitis (UC) is remitting disease with a variable course. Predicting disease relapse after remission is important for the adjustment of medical treatment. Ileocolonoscopy is the best tool for doing this, but due to its invasiveness should be replaced by a method better accepted by the patient. Gastrointestinal ultrasound (GIUS) could be such a method.The PRELAPSE study will include UC patients who have been on maintenance anti-TNF therapy for at one year or more and in clinical remission for the 3 past months at least in two centres, Haukeland University Hospital and Ålesund Hospital. The infrastructure for recruiting these patients has already been established in the BIOSTOP study (Protocol ID no: HMR2016-0.6 and EudraCT (European Clinical Trials Database) no: 2016-001409-18).
Objective:
To study if GIUS or individual US parameters can predict endoscopic relapse at follow up examinations in a group of patients with ulcerative colitis in sustained clinical and endoscopic remission
Study design:
Prospective, longitudinal, explorative, observational multi-centric study for diagnostic accuracy Study population: Adult patients with histo-pathologically confirmed diagnosis of UC between 18 and 80 years of age that have entered the BIOSTOP trial (Trial number: EudraCT: 2016-001409-18) will be considered for inclusion in the proposed study.
Intervention:
All patients will be subjected to trans-abdominal gastrointestinal ultrasound and ileocolonoscopy. Blood and faeces samples will be collected at one time point for measuring relevant inflammatory markers.
Main study parameter: Ultrasound measurements of the intestine of patients with ulcerative colitis Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All patients will be examined repeatedly with gastrointestinal ultrasound (GIUS) and at certain time points with ileocolonoscopy or sigmoidoscopy. As all these procedures already are scheduled as a part of the BIOSTOP study the only extra burden for the patients will be the ultrasound examination. GIUS is a safe procedure that uses high frequency sound waves for the visualization of internal organs. The implementation of GIUS for the assessment of disease activity in UC patients might result in a reduced need for ileocolonoscopy, thereby reducing costs and the burden for patients. Compared to invasive endoscopic procedures GIUS can be performed without preparation, which is an advantage for the patients as treatment decisions can be made without delay. GIUS is also cheaper than ileocolonoscopy, causes little discomfort and has few or no complications.
详细描述
INTRODUCTION AND RATIONALE
1.1 Introduction This protocol describes PRELAPSE, an explorative, prospective, longitudinal observational study of diagnostic accuracy comparing trans-abdominal gastrointestinal ultrasound (GIUS) with ileocolonoscopy for the assessment of disease activity in patients with ulcerative colitis (UC) and with regards relapse as an outcome.
1.2 Background Ulcerative colitis is an inflammatory bowel disease characterized by chronic inflammation mostly limited to the colon mucosa. The diagnostic "gold standard" is ileocolonoscopy and histologic examination of the biopsies. The disease has a variable cause and objective diagnostic criteria are needed to evaluate disease activity (1, 2). Although, the disease is mild in many patients some require biologic treatment with tumor necrosis alpha receptor inhibitors (anti-TNFs). These are expensive drugs with potentially serious adverse effects and patients should have repeated examinations to evaluate treatment effect. Although ileocolonoscopy currently is the best method for objectively assessing disease activity both bowel preparation and the examination causes patients considerable discomfort (3, 4). Therefore, GIUS for the evaluation of disease activity could be a good alternative for treatment follow up in these patients.
In ulcerative colitis the term relapse is commonly used for a flare of symptoms in patients previously in clinical remission. It can either occur in patient without ongoing treatment or during maintenance treatment as a loss of treatment effect (5). Although increased stool frequency, rectal bleeding and abnormal mucosa found by sigmoidoscopy were considered important in defining relapse, a consensus was not reached in the definition in the 2nd ECCO guidelines from 2012 (5). However, it was suggested that the criteria for relapse should be predefined in clinical studies. Commonly, a combination of clinical scores and an endoscopic score has been used for assessment of relapse in clinical trials (6).
The rate of relapse after discontinuing anti-TNF treatment varies between 20-50% during the first year (7-9). For patients receiving treatment with anti-TNF the rates of relapse is about 10-30% (10, 11). Thus the overall risk of relapse in both populations is quite high. A strategy for detecting relapse in the patients in an objective manner without discomfort and lower cost and risk is warranted.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A confirmed diagnosis of ulcerative colitis
- •Six-point Mayo score ≤ 1
- •Two consecutive faecal calprotectin tests <200 mg/kilogram
- •Male or non-pregnant, non-nursing female
- •>18 years of age at inclusion
- •Patients treated for minimum 1 year with first-line anti-tumor necrosis factor (TNF) treatment in sustained clinical remission during the last 3 months
- •Subject capable of understanding and signing an informed consent form
排除标准
- •Discontinuation of systemic 5-acetylsalicylic acid (ASA) or immunomodulatory therapy or other medication that could affect disease activity during the last 3 months prior to randomization
- •Any treatment of systemic corticosteroids due to disease exacerbation during the last 3 months (i.e. patients being in steroid free clinical remission.
- •Patients on anti-TNF monotherapy with intolerance to both 5-ASA and immunomodulatory therapy
- •Change in the anti-TNF treatment during the last 3 months due to disease related factors, not including dose/frequency adjustments due to drug concentration measurements
- •Use of any second-line anti-TNF medication irrespective of reason for stopping first-line anti-TNF
- •Previous failed attempts of anti-TNF discontinuation of more than 4 months' duration, with the exception of discontinuation due to pregnancy
- •Detection of anti-TNF antibodies in moderate-high titers prior to randomization
- •Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol impossible
- •Pregnancy
- •Breastfeeding
- •Participation in any other investigational medicinal Product (IMP) studies
结局指标
主要结局
Endoscopic relapse
时间窗: Follow up period (24 months)
Endscopic relapse defined as a MAYO endoscopic subscore ≥2
次要结局
- Clinical relapse(Follow up period (24 months))
- Interobserver variation(Follow up period (24 months))