The Study of the Optimal Treatment Strategy for Patients With Gastrointestinal Bleeding Due to Gastrointestinal Vascular Malformation: a Randomized, Double Blind, Placebo Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- The primary end point is defined as the patients whose rebleeds decrease from baseline by ≥ 50% at 12 months
研究概览
简要总结
Background: Repeated episodes of bleeding from gastrointestinal vascular malformations refractory to endoscopic or surgical therapy often pose a major therapeutic challenge.
Methods: The investigators will perform a randomized, double blind, placebo controlled study of thalidomide as a retreatment therapy for recurrent gastrointestinal bleeding due to vascular malformation. Patients with failure of first course treatment of thalidomide will be randomly grouped, prescribed a second four-month course regimen of 25 mg of thalidomide or placebo orally four times daily. All patients will be monitored for at least one year. The primary end point is defined as the patients whose rebleeds decrease from baseline by ≥ 50% at 12 months and the cessation of bleeding. Rebleeding is defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment. Secondary outcomes include the participants dependent on blood transfusions and changes from baseline in transfused packed red cell units, bleeding episodes, and hemoglobin levels at 12 months. Statistical significance is defined at P < 0.05.
详细描述
Protocol Description:
This is an exploratory, randomized, double blind, placebo controlled study of thalidomide for retreatment patients with failure of first course thalidomide treatment for recurrent gastrointestinal bleeding from vascular malformations. Informed consent will be taken from all subjects and the Institute Ethics Committee approved the study protocol. All procedures are in accordance with the Declaration of Helsinki. The study is not supported by pharmaceutical funding.
Study design and Intervention:
From Dec. 2014 to Nov. 2015, patients with failure of first course thalidomide treatment and repeated at least four episodes of chronic gastrointestinal bleeding a year due to vascular malformations identified by oesophagogastroduodenoscopy, capsule endoscope or double-balloon endoscope will be enrolled (according our enrollment criteria).
The patients will be randomly assigned to receive a second four-month course of 25 mg of thalidomide or placebo at daily time 6 a.m.,12 noon,6 p.m. and 10 p.m., respectively.
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
- 35 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 35-85 years; women are post-menopausal, post-tubal ligation, or on some form of birth control like long-term laying up contraceptive ring or using condom;
- •Patients with failure of first course treatment of thalidomide, which means rebleeds decreased from baseline by< 50% at 12 months follow up ;
- •History of at least six documented gastrointestinal bleeding episodes in the year prior first course thalidomide treatment, which are refractory or inaccessible to endoscopic therapy or surgical ectomy; so, patients should have at least four episodes of gastrointestinal bleeding a year prior our study;
- •Confirmed diagnosis of vascular malformation by esophagogastroduodenoscopy (EGD), capsule endoscope (CE), double-balloon endoscope (DBE), or colonoscopy, but no obvious infectious, neoplastic, or other specific diagnosis;
- •Angiodysplasia at endoscopy characterized by focal or diffused venous/capillary lesions presenting as bright red ectatic vessels or pulsatile red protrusions, with surrounding venous dilatation or patchy erythema with or without oozing;
- •Endoscopic appearance of GAVE (also known as watermelon stomach), indicated by longitudinal antral folds converging on the pylorus, containing visible columns of tortuous red ecstatic vessels.
排除标准
- •Patients are excluded if first course treatment of thalidomide is effective, which means rebleeds decreased from baseline by ≥ 50% at 12 months follow up;
- •if they have cirrhotic or portal hypertension gastropathy; severe co-morbidities of cardiac, pulmonary, renal, liver, hematological, rheumatologic disorders, or uncontrollable diabetes mellitus or hypertension;
- •if they have a history of severe bilateral peripheral neuropathy or seizure activity, thromboembolic disease, known thalidomide allergy;
- •if they have a history of treatment with any dose of systemic or oral topical corticosteroids or aspirin, NSAIDs, anti-platelet drugs, anticoagulants, or Chinese medications (with salicylates), gingko, or Echinacea, or other putative immunomodulators or anti-angiogenic agents;
- •Currently pregnant or lactating or currently undergoing systemic cancer chemotherapy or receiving radiation
研究组 & 干预措施
Thalidomide Retreatment Group
干预措施: Thalidomide (Drug)
Placebo Group
干预措施: Placebo (Other)
结局指标
主要结局
The primary end point is defined as the patients whose rebleeds decrease from baseline by ≥ 50% at 12 months
时间窗: 12 months
The primary end point is defined as the patients whose rebleeds decrease from baseline by ≥ 50% at 12 months. Reduction of rebleeds = \[(total bleeding episode at 12 months - total bleeding episodes at a year before randomization)/total bleeding episodes at a year before randomization(baseline)\]\*100%. Rebleeding is defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment.
次要结局
- Change From Baseline in Hemoglobin (Hb) Level at 12 Months(12 months)
- Change From Baseline in Bleeding Episodes at 12 Months(12 months)
- Participants Dependent on Blood Transfusions(12 months)
- Cessation of Bleeding(12 months)
- Change From Baseline in Total Transfused Red Cell Requirements at 12 Months(12 months)
研究者
Zhizheng Ge
Shanghai Institute of Digestive Disease，Renji Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai Jiao Tong University School of Medicine