Phase 3 study to investigate the efficacy and safety of the oral FXIa inhibitor Asundexian (BAY 2433334) compared with placebo in participants after an acute non-cardioembolic ischemic stroke or high-risk TIA 

Researchers are looking for a better way to prevent an ischemic stroke which occurs when a blood clot travelled to the brain in people who within the last 72 hours had:

• an acute stroke due to a blood clot that formed outside the heart (acute non-cardioembolic ischemic stroke), or
• TIA/mini-stroke with a high risk of turning into a stroke (high-risk transient ischemic attack), and who are planned to receive standard of care therapy. Acute ischemic strokes or TIA/mini-stroke result from a blocked or reduced blood flow to a part of the brain. They are caused by blood clots that travel to the brain and block the vessels that supply it. If these blood clots form elsewhere than in the heart, the stroke is called non-cardioembolic. People who already had a non-cardioembolic stroke are more likely to have another stroke. This is why they are treated preventively with an antiplatelet therapy, the current standard of care. Antiplatelet medicines prevent platelets, components of blood clotting, from clumping together.

Anticoagulants are another type of medicine that prevents blood clots from forming by interfering with a process known as coagulation (or blood clotting).

The study treatment asundexian is a new type of anticoagulant currently under development to provide further treatment options. Asundexian aims to further improve the standard of care without increasing the risk of bleeding.

The main purpose of this study is to learn whether asundexian works better than placebo at reducing ischemic strokes in participants who recently had a non-cardioembolic ischemic stroke or TIA/mini-stroke when given in addition to standard antiplatelet therapy. A placebo is a treatment that looks like a medicine but does not have any medicine in it.

Another aim is to compare the occurrence of major bleeding events during the study between the asundexian and the placebo group. Major bleedings have a serious or even life-threatening impact on a person’s health.

Dependent on the treatment group, the participants will either take asundexian or placebo as tablets once a day for at least 3 months up to 31 months.

Approximately every 3 months during the treatment period, either a phone call or a visit to the study site is scheduled on an alternating basis. In addition, one visit before and up to two visits after the treatment period are planned.

More information

Intensive are units (ICUs) provide minute by minute monitoring, life support interventions like mechanical ventilation, and potent medications designed to support a person through catastrophic,
life-threatening illnesses. However, these interventions are resource intensive and they carry considerable risks.

In this complex and unique setting, it is imperative that the care provided in ICUs beguided by trustworthy scientific evidence, and that the process whereby science informs care be able to evolve through continuous learning, innovation, and improvement.

This project will shed light on what separates us from realizing a learning critical care health system in Canada. Specifically, it will strengthen our understanding of who is admitted to Canadian ICUs, which interventions they receive, and where research may be embedded into care. The ultimate objective of a learning critical care health system is to generate new knowledge and implement it into practice efficiently and rapidly.

Treatment of Brain Arteriovenous Malformations  (AVM)

The objectives of this study and registry are to offer the best management possible for patients with brain arteriovenous malformations (AVMs) (ruptured or unruptured) in terms of long-term outcomes, despite the presence of uncertainty. Management may include interventional therapy (with endovascular procedures, neurosurgery, or radiotherapy, alone or in combination) or conservative management.

The trial has been designed to test a) whether medical management or interventional therapy will reduce the risk of death or debilitating stroke (due to hemorrhage or infarction) by an absolute magnitude of about 15% (over 10 years) for unruptured AVMs (from 30% to 15%); and, b) to test if endovascular treatment can improve the safety and efficacy of surgery or radiation therapy by at least 10% (80% to 90%).

ENDOVASCULAR ACUTE STROKE INTERVENTION TANDEM OCCLUSION STUDY (EASI_TOC)

A trial of acute cervical internal carotid artery stenting during endovascular thrombectomy for anterior circulation stroke. 

Patients with tandem occlusion or tandem lesion (TL), that is, stroke with an acute intracranial anterior circulation occlusion and an ipsilateral cervical ICA (c-ICA) high-grade stenosis or occlusion, constitute about 15-20% of patients undergoing endovascular thrombectomy (EVT).

However, the optimal treatment of acute stroke patients with TL remains uncertain, as relatively few patients with TL were included in the major randomized controlled trials of EVT and management of the c-ICA was generally not specified by protocol nor analyzed post-hoc.

Recent large multi-centre retrospective cases series suggest that acutely stented patients may have more favorable outcomes than patients treated with angioplasty alone or those with no acute ICA intervention, but high quality randomized trial data are lacking.

EASI-TOC, a phase 3, academic multi-centre, controlled trial (PROBE design) with embedded pilot phase, will seek to determine if in patients undergoing acute intracranial thrombectomy for anterior circulation stroke with concurrent ipsilateral symptomatic high-grade (≥70%) atherosclerotic stenosis or occlusion of the extracranial ICA, endovascular ICA revascularization with stenting is superior to intracranial thrombectomy alone with regards to functional outcome at 90 days. Patients will be randomized to Acute stenting or No acute stenting (1:1 allocation).

A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Nerinetide in Participants with Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis

The purpose of this study is to test if a single dose of nerinetide can reduce neurological disability in people who have had a stroke and who are selected for endovascular therapy.

For this study, 1020 male and female participants will be recruited at hospitals around the world. The participants will be aged 18 years and older.

EVOLVE-Cog: A prospective cohort study of the cognitive and neuropsychiatric effects of iatrogenic brain infarcts and their prevention by acetylsalicylic acid

Patients often end up with tiny strokes after surgery or minimally invasive procedures, like coiling for brain aneurysms. These tiny strokes can be seen on MRI scans. When they are caused by a procedure, they are termed “iatrogenic”. While we don’t know much about their effects in otherwise healthy people, we know that small strokes can cause memory problems when they build up over time in older people with vascular disease. Recent studies have indicated that iatrogenic strokes can cause similar problems, but no treatments have been shown to help with these problems. 

A randomized controlled trial, EVOLVE, is testing whether taking acetylsalicylic acid (ASA, also called aspirin) will reduce the number of strokes after aneurysm coiling. We want to follow these patients for up to a year after coiling to check whether treatment with ASA also results in better memory and mental health. All patients in the trial will have a brain MRI 12-48 hours after coiling.

For our study, we will check the patients for temporary confusion, also called delirium, that can happen after operations. We will also do detailed tests of memory, thinking, and mental health before, shortly after, and up to 1 year after coiling. We will ask patients about their quality of life. We will ask their care partners about how the patients are doing in their daily life. We think that patients getting ASA will do better on the tests and have delirium less often. Based on our prior work, we also expect that patients with more iatrogenic strokes on their brain scan will do worse than those with fewer or no strokes.

Our study will provide the most detailed knowledge of long-term effects of iatrogenic strokes until now. If we find that patients taking ASA do better on our tests, this will help change how we manage thousands of patients treated with procedures like coiling around the world. By understanding the effects of iatrogenic strokes, we can also become better at testing treatments to prevent them.