Phase II, Randomized, Crossover, Single Blind, Safety Trial of DABIGATRAN Versus ASA for Preventing Ischaemic Brain Lesions in Patients Affected by CADASIL
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Number of microbleeds on MRI
研究概览
简要总结
This study is a Phase II, randomized, crossover trial designed to compare one fixed dose of dabigatran with open-label use of ASA in patients affected by CADASIL; the study is a safety trial, and the primary objective is to assess that dabigatran is not less safe than ASA in subjects with CADASIL.
详细描述
The primary endpoint is the number of microbleeds, as measured by MRI, at 90 days of follow up.
The study is based on the hypothesis that drugs inhibitor of the thrombin is more effective than ASA in preventing vessel obstruction. The rationale behind the study is based on the assumption that: a) the formation of microthrombi is relevant to the clinical expression of the CADASIL disease, and b) thrombin inhibitors are more effective than antiplatelet drugs in preventing lesions by microvessel obstruction.
Eligible patients will be randomized into one of the 2 treatment groups:
- One week wash-out (W1), Dabigatran one tablet 100mg twice a day for 12 weeks, a second one week wash-out (W2), treatment with ASA one tablet of 100mg/day once a day for 12 weeks;
- The same scheme repeated with reversed sequence No initial wash-out week will be required for patients in group 2 already treated with ASA.
Clinical and instrumental evaluations will be carried out during the first (W1) and second wash-out weeks (W2), and at the end of the study (during the week that follows the second treatment regimen (W3). Each evaluation will consist of physical examination, blood tests and MRI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
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 aged 18 years or older diagnosed with CADASIL according genetic test will be eligible.
排除标准
- •Treatment with antiplatelet drugs for a condition different from CADASIL;
- •conditions associated with an increased risk of bleeding (major surgery within the previous month, planned surgery or intervention within the next 3 months;
- •history of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding;
- •gastrointestinal hemorrhage within the past year;
- •symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days; hemorrhagic disorder or bleeding diathesis;
- •need for anticoagulant treatment of disorders other than atrial fibrillation; fibrinolytic agents within 48 hours of study entry; uncontrolled hypertension (systolic blood pressure greater than 180 mm Hg and/or diastolic blood pressure greater than 100 mm Hg);
- •recent malignancy or radiation therapy (within 6 months) and not expected to survive 3 years; severe renal impairment (estimated creatinine clearance 30 mL/min or less);
- •active infective endocarditis;
- •active liver disease (including but not limited to persistent ALT, AST, Alk Phos greater than twice the upper limit of the normal range; active hepatitis C (positive HCV RNA);
- •active hepatitis B (HBs antigen +, anti HBc IgM +), active hepatitis A);
- •women who are pregnant or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study.
研究组 & 干预措施
Dabigatran
干预措施: Dabigatran (Drug)
Antiplatelets
干预措施: Antiplatelets (Drug)
结局指标
主要结局
Number of microbleeds on MRI
时间窗: Six Months
Primary endpoint is defined as the difference in number of microbleeds on MRI images taken at the end of the 2 treatments (i.e, during W2 and W3). Secondary endpoint is major bleeding. The neuroradiologists (or trained neurologists) who will examine the images on MRI will be blind to treatment.
次要结局
- Major bleeding(Six Months)