A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of Efficacy of Thalidomide for Refractory Small Intestinal Bleeding From Vascular Malformation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 150
- 试验地点
- 10
- 主要终点
- effective response rate
研究概览
简要总结
Gastrointestinal vascular malformation (GIVM), which is an important cause of acute or chronic gastrointestinal bleeding, currently lacks of effective treatment. The investigators' previous study first confirmed thalidomide treatment of GIVM bleeding was safe and effective. This prospective multi-center randomized controlled clinical trial intends to investigate the efficacy of thalidomide to the recurrent small intestinal hemorrhage due to GIVM.
详细描述
This multi-institutional clinical trial investigates the efficacy of thalidomide to the recurrent small intestinal hemorrhage due to GIVM. Patients with annual average bleeding 4 times or more and lesions located in the small intestine which are not suitable for endoscopic therapy will be randomly assigned to receive A(25mg,Thalidomide，qid), B(25mg, Thalidomide, bid& placebo bid ) or placebo(deferred treatment group) for 4 months. The primary endpoints were the effective response of patients with ≥50% reduction of numbers of bleeding episodes, followed by rate of cases with cessation of bleedin, the difference in blood transfusion, hospitalization, transfusion volume of red cell, average bleeding duration, average hemoglobin level, yearly hospitalization times, average hospital stay and yearly bleeding episodes. This study will be done at 10 centers in China.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects voluntarily signed the informed consent after the nature and the specific procedures of the trial has been verbally explained; they have the opportunity to ask questions.
- •Chinese nationality;
- •Female or male subjects aged 18-75 years. Female subjects must be menopausal or have undergone sterilization such as tubal ligation and hysterectomy, or have no plan to give birth recently and agree to take contraceptive measures such as contraceptive drugs, intrauterine physical birth control rings or contraception condoms; or men must have undergone sterilization or do not plan to have a child recently and agree to take contraceptive measures such as contraceptive drugs, or contraception condoms. These criteria are set to eliminate the risk of subjects of child bearing potential.
- •The subjects must have been diagnosed, by capsule endoscopy and / or balloon-assisted enteroscopy, with small intestinal vascular malformation lesions which are unsuitable or inaccessible to endoscopic therapy or surgical antrectomy. Subjects with persistent, recurrent bleeding, ≥ 4 episodes of overt or occult bleeding over last year.
排除标准
- •Subjects with esophageal varices from cirrhosis of the liver; those with uncontrolled hypertension or hyperglycemia (or diabetics who are being treated with insulin), or those with severe heart (e.g., uncontrolled angina pectoris and / or myocardial infarction, congestive heart failure, etc.), respiratory failure, or renal failure with creatinine (Cr) or blood urea nitrogen (BUN) > 2 times the upper limit of normal (ULN), pancreatic or hepatic disease with abnormal hepatic function with alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin (TBil) > 2 times ULN 3 months before the enrollment, or those with any other diseases that are not suitable for the study as judged by the Investigator;
- •Subjects with a history of severe peripheral neuropathy or seizures, or a history of thromboembolic disease;
- •Subjects who need to continuously use non-steroidal anti-inflammatory drugs, anticoagulants, antiplatelets, acetylsalicylic acid preparations, or Chinese herbal medicines containing ginkgo and echinacea; or those who need to receive other anti-angiogenic drugs for a long time;
- •Subjects with white blood cell counts persistently <3.5 * 10^9 / L;
- •Subjects with a history of small bowel resection;
- •Subjects known or suspected to be allergic to any component of thalidomide；
- •Subjects with severe gastrointestinal bleeding that is life-threatening and requires immediate surgical treatment;
- •Subjects who have previously received thalidomide for gastrointestinal bleeding 30 days before the enrollment;
- •Alcohol and / or substance abusers with addiction or dependence, or those with poor compliance as judged by a doctor;
- •Subjects who participated in other clinical trial 6 months before enrollment;
- •Subjects without legal capacity or self-awareness.
研究组 & 干预措施
placebo -controlled Group
Generic name:Thalidomide Placebo Dosage form:tablet, Placebo Dosage:Placebo Frequency: Placebo, QID, Oral Duration:120 days
干预措施: placebo (Drug)
Thalidomide Group（50mg）
Generic name:Thalidomide Dosage form:tablet, 25mg&Placebo Dosage:50mg/day Frequency: 25mg BID &Placebo, BID, Oral Duration:120 days
干预措施: Thalidomide (50mg) (Drug)
Thalidomide Group（100mg）
Generic name:Thalidomide Dosage form:tablet, 25mg Dosage:100mg/day Frequency: 25mg, QID, Oral Duration:120 days
干预措施: Thalidomide (100mg) (Drug)
结局指标
主要结局
effective response rate
时间窗: First 1-year follow-up versus the 1-year Observation Period.
the proportion of patients with "effective treatment, patients with ≥50% reduction of numbers of bleeding episodes after treatment during the First 1-year follow-up versus the 1-year Observation Period.
次要结局
- overall rate of cases with cessation of bleeding(First 1-year follow-up versus the 1-year Observation Period.)
- change in yearly hospitalization times(First 1-year follow-up versus the 1-year Observation Period.)
- change in the transfusion volume of red cell(First 1-year follow-up versus the 1-year Observation Period.)
- rate of cases requiring blood transfusion(First 1-year follow-up versus the 1-year Observation Period.)
- rate of cases requiring hospitalizations due to bleeding(First 1-year follow-up versus the 1-year Observation Period.)
- change in average bleeding duration(First 1-year follow-up versus the 1-year Observation Period.)
- change in average hemoglobin level(First 1-year follow-up versus the 1-year Observation Period.)
- change in average hospital stay(First 1-year follow-up versus the 1-year Observation Period.)
- change in yearly bleeding episodes(First 1-year follow-up versus the 1-year Observation Period.)
研究者
Zhizheng Ge
Director of digestive endoscopy center of Renji hospital
Shanghai Jiao Tong University School of Medicine