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

NCT ID: NCT04192955

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-14
• Study Completion Date: 2024-12-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Acetyl Salicylate

Intervention Type: DRUG

Tablets

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.

Group Type: PLACEBO_COMPARATOR

Acetyl Salicylate

Intervention Type: DRUG

Tablets

Interventions

Acetyl Salicylate

Tablets

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohammed A Almekhlafi, MD MSc FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Mayank Goyal, MD PhD FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Linda Andersen, PhD

Role: STUDY_DIRECTOR

University of Calgary

Craig Doram, PEng

Role: STUDY_DIRECTOR

University of Calgary

Locations

Foothills Medical Center

Calgary, Alberta, Canada

Site Status: RECRUITING

U of Alberta

Edmonton, Alberta, Canada

Site Status: RECRUITING

Dalhousie University

Halifax, Nova Scotia, Canada

Site Status: RECRUITING

McMaster University

Hamilton, Ontario, Canada

Site Status: RECRUITING

Toronto St Michael's Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Toronto Western Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

McGill University

Montreal, Quebec, Canada

Site Status: RECRUITING

University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status: RECRUITING

Centre Hospitalier Régional Universitaire de Tours

Tours, Centre-Val de Loire, France

Site Status: RECRUITING

Countries

Canada; France

Central Contacts

Mohammed A Almekhlafi, MD MSc FRCPC

Role: CONTACT

mohammed.almekhlafi1@ucalgary.ca

403-944-3458

Karla Ryckborst, RN BN CCRP

Role: CONTACT

karla.ryckborst@albertahealthservices.ca

Facility Contacts

Role: primary

4039441110

Dr Alim Mitha, MD FRCSC

Role: backup

Cian O'Kelly, MD FRCSC

Role: primary

Adrienne Weeks, MD, PhD, FRCSC

Role: primary

BRIAN VAN ADEL, MD, PhD, FRCPC

Role: primary

Aditya Bharatha, MD FRCPC

Role: primary

Ronit Agid, MD, FRCPC

Role: primary

Maria Cortes, MD

Role: primary

Michael Kelly, MD, PhD, FRCSC, FACS, FAANS

Role: primary

Grégoire Boulouis, MD-PhD

Role: primary

Other Identifiers

Version 2.0

Identifier Type: -

Identifier Source: org_study_id