Multicentre, Controlled, Randomised, Investigator-Blinded, Comparative Study of Oral Mesalazine 4g Once Daily Versus Mesalazine 4g in Two Divided Doses in Patients With Active Ulcerative Colitis.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 206
- 试验地点
- 46
- 主要终点
- Primary efficacy criterion: remission after 8 weeks of treatment, defined on the basis of the UC-DAI score less than or equal to 1
研究概览
简要总结
The purpose of this study was to demonstrate that mesalazine 4g orally per day once daily (QD) is non-inferior to the reference regimen, mesalazine 4g per day in two divided doses (BID) (2g x 2 per day), in patients with active ulcerative colitis (UC) treated for 8 weeks, in terms of remission evaluated with the Ulcerative Colitis Disease Activity Index (UC-DAI) score and defined as less than or equal to 1. Both groups (4g QD and 2gx2) received an enema containing 1g of mesalazine at bedtime during the initial 4 weeks.
Participants in remission at week 8 received an additional 4 weeks of maintenance therapy with 2g oral mesalazine once a day. Participants who did not achieve remission at Week 8 completed the study at week 8.
详细描述
A key element in therapeutic response in UC is treatment compliance. In daily practice, compliance of UC patients with 5-Amino Salicylic Acid (5-ASA) treatment appears mediocre, particularly in maintenance therapy. Poor or non-existent compliance affects not only treatment response but also disease progression.
An inverse relationship has been found between the number of daily doses prescribed and treatment compliance. Thus, reduction to a single daily dose of mesalazine is a major factor likely to significantly increase treatment compliance.
Reducing the dosing rate to a single daily dose for 8 weeks constitutes a simple method of improving treatment compliance but it is necessary to demonstrate at least equivalent efficacy compared to the twice daily dosing which is the reference regimen. This study was designed to show that mesalazine 4g once daily is at least as effective as mesalazine 4g in two divided doses per day in patients with mild to moderate ulcerative colitis after 8 weeks of treatment with a better compliance. To improve remission, both groups received an enema during the first 4 weeks, as usually done in current practice.
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
- Single (Investigator)
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
- •Patients will be included if they comply with the following inclusion criteria determined at baseline, prior to first drug administration:
- •Aged over 18 years.
- •Newly diagnosed or relapsing mild to moderate ulcerative colitis with disease extension beyond rectum (of at least 12-18 cm from the anorectal junction). All patients must have had at least one total colonoscopy in their disease history (within the previous 5 years).
- •Disease activity will be assessed on the 15 days before inclusion and according to ulcerative colitis disease activity index (UC-DAI) score. The UC-DAI score will be from 3 to 8 (mild: 3-5 or moderate: 6-8).
- •Men or non pregnant women.
- •Women with childbearing potential must be using a contraceptive method judged effective by the investigator.
- •Oral maintenance treatment with azathioprine or 6-mercaptopurine (taken for at least 6 months at stable dose and continued at the same dose throughout the study) is permitted.
- •Informed consent given.
排除标准
- •The patients will not be included in the study if one of the following exclusion criteria is fulfilled at baseline, prior to first drug administration:
- •Proctitis (less than 12-18 cm from the anorectal junction).
- •Previous colonic surgery.
- •Previously failed to respond to steroids within the previous year.
- •Non-response to rectal 5-Amino Salicylic Acid (5-ASA) therapy or to oral 5-ASA therapy at a dose > 3g/day for induction of remission within the previous year.
- •Current relapse lasting more than 6 weeks (for patient recently diagnosed the period of 6 weeks runs from the endoscopic diagnosis)(from what patient says).
- •Severe/fulminant ulcerative colitis.
- •Evidence of other forms of inflammatory bowel disease or infectious disease.
- •Allergy to aspirin or salicylate derivatives.
- •The following treatment will be forbidden during the study (if present at selection, a wash-out will be necessary):
- •Loperamide and other antidiarrheal agents, mucilages, antibiotics: 1 week wash-out.
- •Oral steroids: 4 weeks wash-out.
- •Rectal steroids: 2 weeks wash-out
- •Repeated treatment (> 3days of use) of non steroidal anti-inflammatory drugs (NSAID) oral or rectal route: 1 week wash-out (aspirin ≤ 325 mg/day used for cardioprotection is allowed).
- •Sulfasalazine > 4g/day or mesalazine or 4-ASA at a higher dose than what is permitted in the local formulary or standard care for maintenance treatment: 4 weeks wash-out
- •Immunomodulating/suppressing drugs: 3 month for wash out (except for patients maintained on azathioprine or 6-mercaptopurine -see above).
- •Known significant hepatic or renal function abnormalities.
- •Moderate/severe abnormal renal, hepatic or blood count tests defined as: creatinine plasma value > 1.5 x Upper Limit of Normal (ULN) or white blood cells < 3500/mm˄3 or > 15000/mm˄3 or Platelets < 100000/mm˄3 or > 800000/mm˄3 or aspartate aminotransferase/alanine Aminotransferase (ASAT/ALAT) > 3 x ULN or Gamma glutamyl transpeptidase (GGT)/Alkaline Phosphatase's > 3 x ULN (Primary Sclerosing Cholangitis is not an exclusion criteria).
- •History or physical examination findings indicative of active alcohol or drug abuse,
- •Pregnancy or breast-feeding,
- •History of disease, including mental/emotional disorder, that might interfere with their participation in the study,
- •Participation in another clinical study in the last 3 months.
- •Inability to comply with the protocol requirements.
- •Inability to fill in the diary cards.
研究组 & 干预措施
Mesalazine once/day
Participants received 4g oral Mesalazine once a day (2 sachets of prolonged release granules) for 8 weeks during the induction period. In addition, participants received a liquid enema of 1g Mesalazine once a day at bedtime for the first 4 weeks. Participants who were in remission at Week 8 received oral mesalazine 2g once daily (1 sachet/day) for an additional 4 weeks (maintenance period).
干预措施: Mesalazine slow-release granules (Drug)
Mesalazine once/day
Participants received 4g oral Mesalazine once a day (2 sachets of prolonged release granules) for 8 weeks during the induction period. In addition, participants received a liquid enema of 1g Mesalazine once a day at bedtime for the first 4 weeks. Participants who were in remission at Week 8 received oral mesalazine 2g once daily (1 sachet/day) for an additional 4 weeks (maintenance period).
干预措施: Mesalazine liquid enema (Drug)
Mesalazine twice/day
Participants received oral mesalazine 4 g per day in two divided doses (1 sachet prolonged release granules twice a day) for 8 weeks during the induction period. In addition, participants received a liquid enema of 1g Mesalazine once a day at bedtime for the first 4 weeks. Participants who were in remission at Week 8 received oral Mesalazine 2g (one sachet) once a day for an additional 4 weeks (maintenance period).
干预措施: Mesalazine slow-release granules (Drug)
Mesalazine twice/day
Participants received oral mesalazine 4 g per day in two divided doses (1 sachet prolonged release granules twice a day) for 8 weeks during the induction period. In addition, participants received a liquid enema of 1g Mesalazine once a day at bedtime for the first 4 weeks. Participants who were in remission at Week 8 received oral Mesalazine 2g (one sachet) once a day for an additional 4 weeks (maintenance period).
干预措施: Mesalazine liquid enema (Drug)
结局指标
主要结局
Primary efficacy criterion: remission after 8 weeks of treatment, defined on the basis of the UC-DAI score less than or equal to 1
时间窗: 12 weeks
次要结局
- Time to remission according to patient's diary (normal stool frequency and cessation of bleeding)(At week 4 and week 8)
- Endoscopic assessment(At week 0 and week 8)
- Compliance(Week 8)
- Improvement - based on UC-DAI score(At week 4 and 8)
- Treatment failure is defined as need of other treatment (ie steroids, immunosuppressive or immunomodulating drugs) than those allowed by the protocol, as judged by investigator. Treatment failure will be counted as non-remission.(At week 4 and week 8)
- Clinical remission(At week 4, week 8 and week 12)
- Time to cessation of bleeding(At week 4, week 8 and week 12)
- Clinical variables (stool frequency and bloody stools)(At week 4, 8 and 12 separately)
- Safety(At week 0, week 4, week 8 and week 12)