Evaluating Oral Peri-operative Acetylsalicylic Acid in Subjects Undergoing Endovascular Coiling-only of Unruptured Brain Aneurysms (EVOLVE)
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|ClinicalTrials.gov Identifier: NCT04192955|
Recruitment Status : Recruiting
First Posted : December 10, 2019
Last Update Posted : July 28, 2020
|Condition or disease||Intervention/treatment||Phase|
|Unruptured Cerebral Aneurysm||Drug: Acetyl Salicylate||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||440 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Evaluating Oral Peri-operative Acetylsalicylic Acid in Subjects Undergoing Endovascular Coiling-only of Unruptured Brain Aneurysms(EVOLVE): A Phase 3 Multicenter Randomized Study|
|Actual Study Start Date :||July 14, 2020|
|Estimated Primary Completion Date :||July 2023|
|Estimated Study Completion Date :||October 2023|
Active Comparator: 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.
Drug: Acetyl Salicylate
Placebo Comparator: 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.
Drug: Acetyl Salicylate
- Clinical or silent stroke [ Time Frame: within 2-4 days of completion of the coiling procedure ]Incidence of embolic strokes (clinically or on DWI-MRI)
- Symptomatic stroke [ Time Frame: Day 90 following coiling. ]Clinical thromboembolic events
- Death rate [ Time Frame: within 90 days following coiling ]
- Peri-operative hemorrhagic complication [ Time Frame: within 90 days following coiling ]intracranial hemorrhage, retroperitoneal hematoma, upper or lower gastrointestinal bleeding, or any bleeding stratified as major according to TIMI
- Count of new DWI lesions on post-coiling MRI [ Time Frame: within 2-4 days of completion of the coiling procedure ]
- Total volume of new DWI lesions on post-coiling MRI [ Time Frame: within 2-4 days of completion of the coiling procedure ]
- Frequency of large (> 10 cc volume) strokes on DWI MR. [ Time Frame: within 2-4 days of completion of the coiling procedure ]
- Incidence of cognitive decline on Montreal Cognitive Assessment (MoCA) from baseline to discharge. [ Time Frame: within 2-4 days of completion of the coiling procedure ]
- Incidence of visible thrombus formation during the coiling procedure [ Time Frame: During the procedure ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04192955
|Contact: Mohammed A Almekhlafifirstname.lastname@example.org|
|Contact: Karla Ryckborstemail@example.com|
|Foothills Medical Center||Recruiting|
|Calgary, Alberta, Canada, T2N 2T9|
|Contact: Dr Alim Mitha, MD FRCSC|
|Principal Investigator:||Mohammed A Almekhlafi||University of Calgary|
|Principal Investigator:||Mayank Goyal||University of Calgary|