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Evaluating Oral Peri-operative Acetylsalicylic Acid in Subjects Undergoing Endovascular Coiling-only of Unruptured Brain Aneurysms (EVOLVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04192955
Recruitment Status : Recruiting
First Posted : December 10, 2019
Last Update Posted : July 28, 2020
Sponsor:
Information provided by (Responsible Party):
University of Calgary

Brief 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 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.

Condition or disease Intervention/treatment Phase
Unruptured Cerebral Aneurysm Drug: Acetyl Salicylate Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Aneurysms

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.
Drug: Acetyl Salicylate
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.
Drug: Acetyl Salicylate
Tablets




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. Symptomatic stroke [ Time Frame: Day 90 following coiling. ]
    Clinical thromboembolic events

  2. Death rate [ Time Frame: within 90 days following coiling ]
  3. 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

  4. Count of new DWI lesions on post-coiling MRI [ Time Frame: within 2-4 days of completion of the coiling procedure ]
  5. Total volume of new DWI lesions on post-coiling MRI [ Time Frame: within 2-4 days of completion of the coiling procedure ]
  6. Frequency of large (> 10 cc volume) strokes on DWI MR. [ Time Frame: within 2-4 days of completion of the coiling procedure ]
  7. 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 ]
  8. Incidence of visible thrombus formation during the coiling procedure [ Time Frame: During the procedure ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  1. 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.
  2. Dissecting or mycotic brain aneurysm.
  3. Any ongoing ischemic symptoms such as transient ischemic attacks, minor strokes, or stroke-in-evolution within 2 weeks before randomization.
  4. Allergy or contraindication to ASA.
  5. Unable to take study drug orally for any reason.
  6. Subjects already taking single or dual antiplatelet, warfarin, or any of the non-Vitamin K antagonist oral anticoagulants.
  7. Subjects unable to undergo MRI imaging for any reason (e.g., severe claustrophobia or presence of metals).
  8. 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.
  9. Pregnancy or breastfeeding.
  10. Prior enrollment in EVOLVE trial for another aneurysm.
  11. 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.

Information from the National Library of Medicine

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


Contacts
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Contact: Mohammed A Almekhlafi 403-944-3458 mohammed.almekhlafi1@ucalgary.ca
Contact: Karla Ryckborst karla.ryckborst@albertahealthservices.ca

Locations
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Canada, Alberta
Foothills Medical Center Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact    4039441110      
Contact: Dr Alim Mitha, MD FRCSC         
Sponsors and Collaborators
University of Calgary
Investigators
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Principal Investigator: Mohammed A Almekhlafi University of Calgary
Principal Investigator: Mayank Goyal University of Calgary
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Responsible Party: University of Calgary
ClinicalTrials.gov Identifier: NCT04192955    
Other Study ID Numbers: Version 2.0
First Posted: December 10, 2019    Key Record Dates
Last Update Posted: July 28, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Intracranial Aneurysm
Aneurysm
Vascular Diseases
Cardiovascular Diseases
Intracranial Arterial Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Salicylates
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action