- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04192955
Evaluating Oral Peri-operative Acetylsalicylic Acid in Subjects Undergoing Endovascular Coiling-only of Unruptured Brain Aneurysms (EVOLVE)
Evaluating Oral Peri-operative Acetylsalicylic Acid in Subjects Undergoing Endovascular Coiling-only of Unruptured Brain Aneurysms(EVOLVE): A Phase 3 Multicenter Randomized Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Mohammed A Almekhlafi, MD MSc FRCPC
- Phone Number: 403-944-3458
- Email: mohammed.almekhlafi1@ucalgary.ca
Study Contact Backup
- Name: Karla Ryckborst, RN BN CCRP
- Email: karla.ryckborst@albertahealthservices.ca
Study Locations
-
-
Alberta
-
Calgary, Alberta, Canada, T2N 2T9
- Recruiting
- Foothills Medical Center
-
Edmonton, Alberta, Canada
- Recruiting
- U of Alberta
-
Contact:
- Cian O'Kelly, MD FRCSC
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canada
- Recruiting
- Dalhousie University
-
Contact:
- Adrienne Weeks, MD, PhD, FRCSC
-
-
Ontario
-
Hamilton, Ontario, Canada
- Recruiting
- McMaster University
-
Contact:
- BRIAN VAN ADEL, MD, PhD, FRCPC
-
Toronto, Ontario, Canada
- Recruiting
- Toronto Western Hospital
-
Contact:
- Ronit Agid, MD, FRCPC
-
Toronto, Ontario, Canada, Toronto
- Recruiting
- Toronto St Michael's Hospital
-
Contact:
- Aditya Bharatha, MD FRCPC
-
-
Quebec
-
Montréal, Quebec, Canada
- Recruiting
- McGill University
-
Contact:
- Maria Cortes, MD
-
-
Saskatchewan
-
Saskatoon, Saskatchewan, Canada
- Recruiting
- University of Saskatchewan
-
Contact:
- Michael Kelly, MD, PhD, FRCSC, FACS, FAANS
-
-
-
-
Centre-Val De Loire
-
Tours, Centre-Val De Loire, France
- Recruiting
- Centre Hospitalier Régional Universitaire de Tours
-
Contact:
- Grégoire Boulouis, MD-PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Tablets
|
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.
|
Tablets
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
within 2-4 days of completion of the coiling procedure
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Symptomatic stroke
Time Frame: Day 90 following coiling.
|
Clinical thromboembolic events
|
Day 90 following coiling.
|
Death rate
Time Frame: within 90 days following coiling
|
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 thrombolysis in myocardial infarction (TIMI) definition.
|
within 90 days following coiling
|
Count of new DWI lesions on post-coiling MRI
Time Frame: within 2-4 days of completion of the coiling procedure
|
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
|
within 2-4 days of completion of the coiling procedure
|
|
Frequency of large (> 10 cc volume) strokes on DWI MRI
Time Frame: within 2-4 days of completion of the coiling procedure
|
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
|
within 2-4 days of completion of the coiling procedure
|
|
Incidence of visible thrombus formation during the coiling procedure
Time Frame: During the procedure
|
During the procedure
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mohammed A Almekhlafi, MD MSc FRCPC, University of Calgary
- Principal Investigator: Mayank Goyal, MD PhD FRCPC, University of Calgary
- Study Director: Linda Andersen, PhD, University of Calgary
- Study Director: Craig Doram, PEng, University of Calgary
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Intracranial Arterial Diseases
- Aneurysm
- Intracranial Aneurysm
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Salicylates
Other Study ID Numbers
- Version 2.0 (Sponsor)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Unruptured Cerebral Aneurysm
-
Montefiore Medical CenterRecruitingAneurysm Cerebral (Unruptured)United States
-
University Hospitals Cleveland Medical CenterCompletedCerebral Aneurysm Unruptured | Cerebral Aneurysm RupturedUnited States
-
Centre hospitalier de l'Université de Montréal...RecruitingCerebral Aneurysm | Intracranial Aneurysm | Unruptured Cerebral Aneurysm | Brain Aneurysm | Ruptured Cerebral AneurysmCanada
-
Artiria MedicalRecruitingUnruptured Cerebral AneurysmSwitzerland
-
Universidad de AntioquiaCompletedAirway Morbidity | Cerebral Aneurysm | Hemodynamic Instability | Cerebral Aneurysm Unruptured
-
Moscow Regional Research and Clinical Institute...Not yet recruitingUnruptured Cerebral Aneurysm | Ruptured Cerebral Aneurysm
-
Sinomed Neurovita Technology Inc.Xuanwu Hospital, BeijingActive, not recruitingCerebral Aneurysm | Cerebral Aneurysm UnrupturedChina
-
Yonsei UniversityUnknown
-
Yonsei UniversityCompletedUnruptured Cerebral AneurysmKorea, Republic of
-
Shape Memory Medical, Inc.Active, not recruitingRuptured or Unruptured Cerebral AneurysmsChile
Clinical Trials on Acetyl Salicylate
-
Imam Khomeini HospitalTehran Heart CenterUnknownRadiographic Contrast Agent Nephropathy | Chronic Kidney Disease Stage 2Iran, Islamic Republic of
-
University of ThessalyNot yet recruiting
-
National Institute of Neurological Disorders and...Terminated
-
National Institute of Diabetes and Digestive and...Completed
-
Leadiant Biosciences, Inc.National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other collaboratorsActive, not recruiting
-
Sher-E-Bangla Medical CollegeCompleted
-
Minia UniversityUnknown
-
National Institute of Neurological Disorders and...BCN PeptidesCompleted
-
Medical University of South CarolinaCompletedDiabetic Foot | Foot Ulcer | Leg Ulcer | Venous Insufficiency | Varicose Ulcer | Venous Ulcer | Venous Stasis Ulcer | Venous Hypertension UlcersUnited States