Evaluating Oral Peri-operative Acetylsalicylic Acid in Subjects Undergoing Endovascular Coiling-only of Unruptured Brain Aneurysms(EVOLVE): A Phase 3 Multicenter Randomized Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 440
- 试验地点
- 12
- 主要终点
- Clinical or silent stroke
研究概览
简要总结
This trial is a is a prospective, randomized (1:1) placebo-controlled, clinical trial with blinded endpoint assessment of 440 participants with unruptured brain aneurysm planned for endovascular treatment using coiling-only approach (primary coiling or using balloon-assistance but not stenting) to test if oral acetylsalicylic acid (325 mg/ day for a total of 5 days) is superior placebo in preventing clinical and silent strokes. The primary outcome is a clinical or silent stroke at the time of discharge assessed by clinical examination and MRI brain. Participants will return to the clinic or be contacted by phone for the end of study procedures on Day 90 to collect functional outcome data.
详细描述
Endovascular aneurysm treatment has become the mainstay of treatment of unruptured brain aneurysms. Since the introduction of Guglielmi detachable coils in the late 1980s, thousands of procedures are performed annually worldwide. The expanding endovascular armamentarium with the use of balloon-assisted coiling, stents (either in stent-assisted coiling or flow-diversion), and unassisted coiling-only procedures made it possible to treat aneurysms of almost all intracranial locations, shapes, and sizes.
Thromboembolic complications are potential adverse events whenever catheters are introduced into the intracranial arteries. Diagnostic and interventional neurological procedures, such as diagnostic and therapeutic cerebral angiograms may lead to ischemic strokes of varying frequency and severity. Luckily, most of the thromboembolic events do not cause a clinical stroke. Instead, tiny infarction signals are seen on Diffusion-weighted magnetic resonance imaging (DWI MRI) of the brain without neurological signs or symptoms. These are often labelled as silent (or covert) strokes. These imaging surrogates have been used to compare the safety and efficacy of various endovascular procedures and techniques. In a Canadian cohort, heparin bolus during aneurysm coiling was associated with significantly less DWI load on post-coiling MRI. This supports the notion that most of these lesions are caused by thrombi, as opposed to bubbles.
There is limited direction from available guidelines regarding the use of anticoagulation or antiplatelet agents to prevent thromboembolic complications associated with endovascular treatment of brain aneurysms. This resulted in huge variability of the protocols used for anticoagulation and antiplatelet therapies before, during and after coil embolization of brain aneurysms. Most of the current practices are extrapolated from coronary literature.
Platelet inhibition is an effective strategy to minimize the rate of thromboembolism. Antiplatelet treatment has been routinely used before coronary angioplasty to reduce the risk of thromboembolic events. The different action of ASA from that of anticoagulants gives it an additive effect to heparin alone in neuro-interventional procedures. This notion is supported by observations from multiple retrospective and prospective studies.
We will perform a prospective, randomized (1:1) placebo-controlled, clinical trial with blinded endpoint assessment of 440 participants with unruptured brain aneurysm planned for endovascular treatment using coiling-only approach (primary coiling or using balloon-assistance but not stenting) to test if oral acetylsalicylic acid (325 mg/ day for a total of 5 days: 3 days prior and two days after and including the coiling procedure day) is superior placebo in preventing clinical and silent strokes. The primary outcome is a clinical or silent stroke at the time of discharge assessed by clinical examination and MRI brain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, 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
- •Unruptured intracranial aneurysm suitable for coiling-only (primary coiling or balloon-assisted) as a primary treatment.
- •Functionally independent at baseline (modified Rankin scale <3).
- •Informed consent and availability of the subject for the entire study period.
排除标准
- •Planned complex aneurysm treatment including use of any device that requires post-operative antiplatelet therapy (stent-assisted coiling or flow-diverter device), or endovascular vessel sacrifice.
- •Dissecting or mycotic brain aneurysm.
- •Any ongoing ischemic symptoms such as transient ischemic attacks, minor strokes, or stroke-in-evolution within 2 weeks before randomization.
- •Allergy or contraindication to ASA.
- •Unable to take study drug orally for any reason.
- •Subjects already taking single or dual antiplatelet, warfarin, or any of the non-Vitamin K antagonist oral anticoagulants.
- •Subjects unable to undergo MRI imaging for any reason (e.g., severe claustrophobia or presence of metals).
- •Any other medical condition that the site investigator deems would put the subject at excessive risk by participation in the study (e.g. active bleeding, symptomatic peptic ulcer disease, liver or kidney failure, thrombocytopenia or coagulopathy) or an expected life expectancy less than one year, or that would result in an inability to collect radiological outcomes and clinical outcomes at 90 days.
- •Pregnancy or breastfeeding.
- •Prior enrollment in EVOLVE trial for another aneurysm.
- •Participation in another clinical trial of an investigational drug, device or procedure if the subject received the trial drug, device or procedure in the preceding 30 days from the anticipated coiling date.
研究组 & 干预措施
Active
Acetylsalicylic acid (ASA) will be given orally at a dose of 324 mg to be taken daily starting 3 days prior to the planned coiling procedure day, on the procedure day, and for one-day post-procedure.
干预措施: Acetyl Salicylate (Drug)
Control
Lactose100-mg tablets to be taken daily starting 3 days prior to the planned coiling procedure day, on the procedure day, and for one-day post-procedure.
干预措施: Acetyl Salicylate (Drug)
结局指标
主要结局
Clinical or silent stroke
时间窗: within 2-4 days of completion of the coiling procedure
Incidence of embolic strokes (clinically or on DWI-MRI)
次要结局
- Count of new DWI lesions on post-coiling MRI(within 2-4 days of completion of the coiling procedure)
- Frequency of large (> 10 cc volume) strokes on DWI MRI(within 2-4 days of completion of the coiling procedure)
- Incidence of cognitive decline on Montreal Cognitive Assessment (MoCA) from baseline to discharge.(within 2-4 days of completion of the coiling procedure)
- Death rate(within 90 days following coiling)
- Symptomatic stroke(Day 90 following coiling.)
- Total volume of new DWI lesions on post-coiling MRI(within 2-4 days of completion of the coiling procedure)
- Peri-operative hemorrhagic complication(within 90 days following coiling)
- Incidence of visible thrombus formation during the coiling procedure(During the procedure)