Long-term Effects of Thalidomide for Recurrent Gastrointestinal Bleeding Due to Vascular Malformation : An Open-label, Randomized, Parallel Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 主要终点
- Participants Whose Rebleeds Decreased 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 performed a randomized, parallel controlled study of thalidomide as a therapy for recurrent gastrointestinal bleeding due to vascular malformation. Patients with at least six episodes of bleeding in the prior year due to vascular malformation were randomly grouped, prescribed a four-month regimen of either 25 mg of thalidomide or 100 mg of iron orally four times daily, and monitored for at least one year. The primary end point was defined as the patients whose rebleeds decreased from baseline by ≥ 50% at 12 months and the cessation of bleeding. Rebleeding was defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment. Secondary outcomes included the participants dependent on blood transfusions and changes from baseline in transfused packed red cell units, bleeding episodes, bleeding durations, and hemoglobin levels at 12 months. Statistical significance was defined at P < 0.05.
详细描述
Protocol Description:
This is an exploratory, randomized, parallel controlled study of thalidomide for recurrent gastrointestinal bleeding from vascular malformations. Informed consent was taken from all subjects and the Institute Ethics Committee approved the study protocol. All procedures were in accordance with the Declaration of Helsinki. The study was supported by no pharmaceutical funding.
Study design and Intervention:
From Nov. 2004 to Nov. 2007, patients with repeated episodes of chronic gastro-intestinal bleeding due to vascular malformations identified by oesophagogastroduodenoscopy, capsule endoscope or double-balloon endoscope were enrolled (according our enrollment criteria).
The patients were randomly assigned to receive a four-month course of either 25 mg of thalidomide or 100mg iron orally 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
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 40-85 years; women were post-menopausal, post-tubal ligation, or on some form of birth control like long-term laying up contraceptive ring or using condom;
- •History of at least six documented gastrointestinal bleeding episodes in the year prior to randomization, which were refractory or inaccessible to endoscopic therapy or surgical ectomy;
- •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 were excluded if their bleeding history were less than 1 year;
- •if they had cirrhotic or portal hypertension gastropathy; severe co-morbidities of cardiac, pulmonary, renal, liver, hematological, rheumatologic disorders, or uncontrollable diabetes mellitus or hypertension;
- •if they had a history of severe bilateral peripheral neuropathy or seizure activity, thromboembolic disease, known thalidomide or iron allergy, or prior treatment of gastrointestinal bleeding with thalidomide;
- •if they had 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
- •if they were undergoing systemic cancer chemotherapy or receiving radiation.
研究组 & 干预措施
Thalidomide Group
干预措施: Thalidomide (Drug)
Iron-controlled Group
干预措施: Iron (Drug)
结局指标
主要结局
Participants Whose Rebleeds Decreased From Baseline by ≥ 50% at 12 Months
时间窗: baseline and 12 months
The primary end point was defined as the patients whose rebleeds decreased 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 was defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment.
Cessation of Bleeding
时间窗: 52 months
The cessation of bleeding was defined as repeated negative faecal occult blood test (FOBT) (monoclonal colloidal gold color technology) during our observation period. Rebleeding was defined based on a positive FOBT at any visit after treatment.
次要结局
- Change From Baseline in Bleeding Episodes at 12 Months(baseline and 12 months)
- Change From Baseline in Bleeding Duration at 12 Months(baseline and 12 months)
- Participants Dependent on Blood Transfusions(52 months)
- Change From Baseline in Hemoglobin (Hb) Level at 12 Months(baseline and 12 months)
- Change From Baseline in Total Transfused Red Cell Requirements at 12 Months(baseline and 12 months)