Lovastatin for Treatment of Brain Arteriovenous Malformations:a Double-blind, Placebo-controlled Randomized Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 1,244
- 试验地点
- 1
- 主要终点
- Change in the incidence of stroke between two arms
研究概览
简要总结
The purpose of this pilot study is to evaluate the disease-modifying efficacy of lovastatin in patients with brain arteriovenous malformation.
详细描述
Brain arteriovenous malformations are lesions that consist of multiple arteries and veins, connecting as a fistula without intervening normal capillary bed. As the disease progresses, the lesion may cause several adverse clinical events including stroke, seizure or even death. For patients with BAVM deemed unsuitable for invasive treatment or who has elected to defer invasive treatment, it is essential to take effective medical management.
Lovastatin possesses antiinflammatory and antiproliferative actions in human endothelial and vascular smooth muscle cells independent of its lipid-lowing action. These findings suggest that lovastatin may be beneficial for maintaining vascular stability, which may contribute to slowing down the progression of the disease and reducing the incidence of adverse clinical events.
The purpose of this pilot study is to evaluate the safety and disease-modifying efficacy of lovastatin in patients with BAVMs. Participants will be randomly assigned to receive either combination of lovastatin and symptomatic treatment drugs or combination of placebo and symptomatic treatment drugs. Patients will have post-dose safety follow-up visit at 1, 3, 6, and 12 months after the study begins. The changes in clinical outcomes, including lesion volume changes and the rate of stroke, seizure or death, will be evaluated in a period of 2 years.
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
- Double (Participant, 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
- •Patient must have BAVM diagnosed by MRI/MRA, CTA and/or angiogram
- •BAVM deemed unsuitable for invasive treatment OR patient has elected to defer invasive treatment
- •Patient must be 18 years of age or older
- •Sign the informed consent
排除标准
- •Patient has received prior BAVM interventional therapy (endovascular, surgical, radiotherapy)
- •Patient has multiple-foci BAVMs
- •Patient has any form of arteriovenous or spinal fistulas
- •Previous diagnosis of any of the following -
- •Patient was diagnosed with Vein of Galen type malformation
- •Patient was diagnosed with cavernous malformation
- •Patient was diagnosed with dural arteriovenous fistula
- •Patient was diagnosed with venous malformation
- •Patient was diagnosed with neurocutaneous syndrome such as cerebro-retinal angiomatosis (von Hippel-Lindau), encephalo-trigeminal syndrome (Sturge-Weber), or Wyburn-Mason syndrome
- •Patient was diagnosed with BAVMs in context of moya-moya-type changes
- •Patient was diagnosed with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)
- •Contraindication to an HMG-coA-reductase inhibitor
- •History of adverse reaction to HMG-coA-reductase inhibitors (rhabdomyolysis, hepatitis)
- •Use of any cholesterol lowering medication in the previous 12 weeks
- •Uncontrolled medical conditions that could potentially increase the risk of toxicities or complications of this treatment
- •Impaired liver function with aspartate transaminase (AST) or alanine transaminase (ALT) is more than twice limit of normal.
- •Creatine kinase (CK) is more than twice limit of normal.
- •Medications that interfere with the metabolism of lovastatin
- •Gastrointestinal disease that would affect the ability to swallow or take oral medications or absorb them.
- •End stage renal disease (creatinine clearance eGFR <30 mL/min) or history of severe cardiac disease (angina, myocardial infarction or cardiac surgery in preceding two years)
- •Patient has a history of chronic alcohol or drug abuse within 2 years prior to being recruited
- •Patient has known allergy against iodine contrast agents
- •Patient is pregnant or lactating
- •Inability to provide informed consent.
- •Participation in any clinical investigation within 2 months prior to dosing
研究组 & 干预措施
Lovastatin intervention
combination of 40mg/d 12m lovastatin and symptomatic treatment drugs as a treatment strategy for BAVM .
干预措施: Lovastatin (Drug)
placebo
combination of placebo and symptomatic treatment drugs as a treatment strategy for BAVM
干预措施: Placebo (Drug)
结局指标
主要结局
Change in the incidence of stroke between two arms
时间窗: 24 months
Stroke is defined as a clinically symptomatic event (any new focal neurological deficit, seizure, or new-onset headache) that is associated with imaging findings of haemorrhage or infarction. Haemorrhage is defined as fresh intracranial blood on head CT or MRI, or in the cerebrospinal fluid. Infarction is defined as a new ischaemic lesion on cranial CT or MRI (diffusion-weighted, T2-weighted, or fluid-attenuated inversion recovery MRI).
次要结局
- Change in AVM volume from baseline MRI(baseline, 6 months, 12 months, 18 months, 24 months)
- Changes in the incidence of seizures and death between two arms(24 months)
研究者
Dr. Yong Cao
Principal Investigator
Beijing Tiantan Hospital