Unruptured Cerebral AneurysmPhase 3EVOLVENCT04192955
Evaluating Oral Peri-operative Acetylsalicylic Acid in Subjects Undergoing Endovascular Coiling-only of Unruptured Brain Aneurysms
A Phase 3 study testing Acetyl Salicylate in people with Unruptured Cerebral Aneurysm, run by University of Calgary at 9 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unruptured Cerebral Aneurysm
- What is being tested?
- Acetyl Salicylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 440 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 14 Jul 2020to Jul 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Karla Ryckborst, RN BN CCRP contact
9 sites in 2 countries
Canada8 sites, 8 recruiting
- Recruiting
Foothills Medical Center
Calgary, Alberta, T2N 2T9
4039441110
Dr Alim Mitha, MD FRCSC
- Recruiting
U of Alberta
Edmonton, Alberta
Cian O'Kelly, MD FRCSC
- Recruiting
Dalhousie University
Halifax, Nova Scotia
Adrienne Weeks, MD, PhD, FRCSC
- Recruiting
McMaster University
Hamilton, Ontario
BRIAN VAN ADEL, MD, PhD, FRCPC
- Recruiting
McGill University
Montreal, Quebec
Maria Cortes, MD
- Recruiting
University of Saskatchewan
Saskatoon, Saskatchewan
Michael Kelly, MD, PhD, FRCSC, FACS, FAANS
- Recruiting
Toronto St Michael's Hospital
Toronto, Ontario, Toronto
Aditya Bharatha, MD FRCPC
- Recruiting
Toronto Western Hospital
Toronto, Ontario
Ronit Agid, MD, FRCPC
France1 site, 1 recruiting
- Recruiting
Centre Hospitalier Régional Universitaire de Tours
Tours, Centre-Val de Loire
Grégoire Boulouis, MD-PhD
About this study
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
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.
Read the 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.
- Conditions
- Unruptured Cerebral Aneurysm
- Being tested
- Acetyl Salicylate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetyl SalicylateDrug
Tablets
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | 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. Receives: Drug: Acetyl Salicylate |
| Control | Placebo comparator | 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. Receives: Drug: Acetyl Salicylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical or silent stroke
Incidence of embolic strokes (clinically or on DWI-MRI)
Measured: within 2-4 days of completion of the coiling procedure
Secondary outcomes (8)
Symptomatic stroke
Clinical thromboembolic events
Measured: Day 90 following coiling.
Death rate
Measured: within 90 days following coiling
Peri-operative hemorrhagic complication
intracranial hemorrhage, retroperitoneal hematoma, upper or lower gastrointestinal bleeding, or any bleeding stratified as major according to thrombolysis in myocardial infarction (TIMI) definition.
Measured: within 90 days following coiling
Count of new DWI lesions on post-coiling MRI
Measured: within 2-4 days of completion of the coiling procedure
Total volume of new DWI lesions on post-coiling MRI
Measured: within 2-4 days of completion of the coiling procedure
Frequency of large (> 10 cc volume) strokes on DWI MRI
Measured: within 2-4 days of completion of the coiling procedure
Incidence of cognitive decline on Montreal Cognitive Assessment (MoCA) from baseline to discharge.
Measured: within 2-4 days of completion of the coiling procedure
Incidence of visible thrombus formation during the coiling procedure
Measured: During the procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start14 Jul 2020
- Primary completionMar 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unruptured Cerebral AneurysmStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 440 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohammed A Almekhlafi, MD MSc FRCPC, Principal investigator, University of CalgaryMayank Goyal, MD PhD FRCPC, Principal investigator, University of CalgaryLinda Andersen, PhD, Study director, University of CalgaryCraig Doram, PEng, Study director, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04192955
- Sponsor's protocol ID
- Version 2.0
- Acronym
- EVOLVE
- Status last verified
- Aug 2026
- First submitted
- 28 Nov 2019
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04192955
- Acronym / sponsor ID
- EVOLVE / Version 2.0
- Conditions
- Unruptured Cerebral Aneurysm
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 440 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 14 Jul 2020 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 10 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Drug: Acetyl SalicylateAcetylsalicylic 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. |
| Control | Placebo comparator | Drug: Acetyl SalicylateLactose100-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acetyl SalicylateTablets | Drug | Active, Control |
Primary outcome
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)
8 secondary outcomes
Symptomatic stroke
Time frame: Day 90 following coiling.
Death rate
Time frame: within 90 days following coiling
Peri-operative hemorrhagic complication
Time frame: 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
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 MRI
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for Unruptured Cerebral Aneurysm
RecruitingObservational study
A Study of Choydar Flow-Directed Mesh Stent in the Treatment of Unruptured Intracranial Aneurysms
Intracranial Aneurysm
Not yet recruiting
Effect of Bilateral Greater Occipital Nerve Block on Headache After Intracranial Aneurysm Coiling
Intracranial Aneurysm, Postoperative Pain
RecruitingObservational study
Evaluation of Intestinal Microbiota Implication in Ruptured Intracranial Aneurysm
Intracranial Sacciform Aneurysm
Not yet recruitingPhase 4
Efficacy and Safety of Methylprednisolone After Flow-Diverter Stent Implantation in Unruptured Intracranial Aneurysms
Unruptured Intracranial Aneurysms, Cerebrovascular Event
Recruiting
Safety and Efficacy of Endovascular Treatment of Intracranial Aneurysms With Surpass Elite With GUARDian Flow Diverter (GUARD)
Aneurysm, Aneurysm, Intracranial
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Karla Ryckborst, RN BN CCRP contact
Mohammed A Almekhlafi, MD MSc FRCPC principal investigator
University of Calgary
Mayank Goyal, MD PhD FRCPC principal investigator
University of Calgary
Linda Andersen, PhD study director
University of Calgary
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acetyl Salicylate in people with Unruptured Cerebral Aneurysm, run by University of Calgary at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Canada, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohammed A Almekhlafi, MD MSc FRCPC (403-944-3458, mohammed.almekhlafi1@ucalgary.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical or silent stroke (time frame: within 2-4 days of completion of the coiling procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.