Acute Ischemic Stroke

The HOPE-MeVO study aims to evaluate the efficacy and safety of intravenous recombinant human prourokinase (rhPro-UK) in patients with acute ischemic stroke due to medium vessel occlusion presenting 4.5 to 24 hours after stroke onset or last known well. Eligible patients will be selected based on CT perfusion imaging and randomly assigned to receive rhPro-UK plus standard medical treatment or standard medical treatment alone. The primary objective is to determine whether rhPro-UK improves functional outcome at 90 days.

This is a multicenter, open-label, blinded-endpoint, randomized controlled trial comparing super large bore catheter aspiration versus stent retriever thrombectomy as the first-line technique for anterior circulation large vessel occlusion in acute ischemic stroke. Eligible patients with acute ischemic stroke due to internal carotid artery intracranial segment and/or middle cerebral artery M1 occlusion will be randomized 1:1 to receive either aspiration using a super large bore catheter (inner diameter ≥0.080 inch) or stent retriever thrombectomy (allowing balloon guiding catheters or intermediate catheters with inner diameter \<0.080 inch). The primary outcome is the ordinal modified Rankin Scale score at 90 days post-procedure. Key secondary outcomes include the proportion of patients with mRS 0-2 at 90 days, change in NIHSS at 24 hours and 7 days, and various angiographic and safety endpoints. The trial plans to enroll 708 patients across approximately 30 centers in China. The total study duration is 24-36 months, with each patient participating for 3 months.

The goal of this observational study is to learn how the timing of mobilisation after endovascular thrombectomy (EVT) affects complications in patients with acute ischaemic stroke. The main questions it aims to answer are: Does mobilisation approximately 12 hours after EVT, compared to approximately 24 hours after EVT, affect the risk of complications such as access site haematoma (ASH), venous thromboembolism (VTE), infections, and delirium? How common are these complications after EVT, and which factors are associated with increased risk? Participants undergoing EVT as part of their regular stroke care at two hospitals with different mobilisation routines will be followed during their hospital stay. Researchers will collect information about mobilisation timing, complications, clinical assessments, and medical history using case report forms, electronic health records, and national stroke registries.

This trial will evaluate the efficacy and safety of HRS-4029 compared with placebo in participants with acute ischemic stroke (AIS).

The benefit of intravenous tenecteplase for acute ischemic stroke with unknown time of onset, e.g. wake-up stroke, remains uncertain. This randomized study aims to assess the efficacy and safety of intravenous tenecteplase following non-contrast CT screening for acute ischemic stroke with unknown time of onset.

The goal of this Phase I unblinded, dose-escalation trial is to evaluate the safety and tolerability of intra-arterial magnesium sulfate injection after mechanical thrombectomy in patients experiencing acute ischemic stroke. This trial is one of the first trials to look at IA administration of magnesium sulfate into at risk brain tissue in a selective and localized fashion.

The primary objective is to establish the efficacy of intra-arterial (IA) mechanical thrombectomy (MT) with extracranial proximal carotid artery acute stenting versus non-stenting approaches in patients with acute ischemic stroke (AIS) from intracranial vessel occlusion (IVO) in the anterior circulation and have a proximal carotid occlusive disease (occlusion or severe stenosis).

The goal of this observational study is to learn about the effectiveness and safety of antiplatelet and anticoagulant treatments in people with a history of cancer who have acute ischemic stroke. The main questions it aims to answer are: * Are there differences in the risk of another stroke between people receiving antiplatelet treatment and those receiving anticoagulant treatment? * Are there differences in the risk of bleeding between the treatment groups? * Which clinical characteristics, imaging findings, cancer-related factors, and blood test results are associated with treatment outcomes? Participants will: * Receive antiplatelet treatment, anticoagulant treatment, or a combination of both, as selected by their treating physicians during routine clinical care. * Provide clinical information and blood samples for the study. * Complete follow-up assessments approximately 30, 90, 180, and 360 days after the stroke. Researchers will compare recurrent stroke, bleeding, other blood clot-related events, functional recovery, and survival among participants receiving different antithrombotic treatments. The study will not assign or change participants' treatments.

This study is open to adults who had an acute stroke caused by a clot blocking a blood vessel in the brain (acute ischemic stroke). This study is for people who had an acute stroke or woke up with a stroke and were last seen well more than 4.5 hours before joining the study. Participants need to have imaging that shows there is brain tissue that can still be saved. They also should not be planned to receive a procedure to remove the blood clot. The purpose of this study is to find out whether a medicine called tenecteplase helps people recover from an acute stroke. Tenecteplase is already used to treat people within 4.5 hours after they had a stroke. This study tests if tenecteplase also helps if it is given more than 4.5 hours after the stroke. Participants are put into 2 groups randomly, which means by chance. One group gets tenecteplase as a single injection into a vein. The other group receives standard medical practice. Participants have an equal chance of receiving tenecteplase or the standard treatment. Participants are in the study for about 3 months. In the beginning, participants stay in the hospital for about 1 week. During the study, participants have 7 clinical examinations or visits. The last 2 of these visits will likely be done from home, allowing participants to complete certain assessments remotely. Doctors regularly test participants' recovery using a scale that measures the level of disability or dependence in daily activities. The results are compared between the 2 groups to see whether the treatment works. The doctors also check participants' health and take note of any unwanted effects.

The goal of this observational study is to evaluate the role of blood pressure (BPV) variability in patients suffering from acute ischemic stroke. The main questions it aims to answer are: 1. To determine the association of BPV with functional/cognitive outcome after ischemic stroke. 2. To determine a pathophysiologic mechanism of BPV's deleterious effect on functional outcome. 3. To evaluate potential treatment targets to pharmacologically reduce BPV after ischemic stroke.

Patients with acute ischemic stroke caused by distal or medium vessel occlusions (MeVOs) may experience significant disability despite receiving the current standard medical treatment. Although endovascular treatment (EVT) is an established therapy for large vessel occlusions, its benefit in MeVO stroke remains uncertain. The SAIL-MEVO trial is a prospective, multicenter, randomized controlled trial designed to evaluate whether EVT combined with best medical therapy improves functional outcomes compared with best medical therapy alone in selected patients with acute ischemic stroke due to MeVO. Eligible participants will be randomized in a 1:1 ratio to receive either best medical therapy alone or best medical therapy plus EVT using a standardized stepwise approach consisting of aspiration thrombectomy (ADAPT) followed, when necessary, by the SAIL technique (stent retriever-assisted intra-arterial lysis). The primary objective is to determine whether EVT increases the proportion of patients achieving functional independence (modified Rankin Scale score 0-2) at 90 days after stroke. Secondary objectives include assessment of neurological recovery, infarct volume, quality of life, patient-reported outcomes, safety, and procedural outcomes.

Acute ischemic stroke may result in substantial disability despite timely reperfusion therapy because ischemic and reperfusion-related brain injury can continue before, during, and after restoration of blood flow. This investigator-initiated, prospective, multicenter, randomized, open-label, blinded-endpoint trial will evaluate whether a protocolized Stimulation-Temperature-Oxygen-Positioning (STOP) multimodal neuroprotective strategy added to guideline-based reperfusion therapy and stroke-unit care improves 90-day functional outcome compared with standard care alone. A total of 380 adults with acute ischemic stroke treated with intravenous thrombolysis and/or endovascular therapy within 24 hours of symptom onset or last known well will be randomized in a 1:1 ratio to the STOP strategy plus standard care or standard care alone. The STOP strategy comprises transcutaneous auricular vagus nerve stimulation, protocolized normothermia targeting a body temperature of 37.5 °C or lower, high-flow normobaric oxygen, and dynamic head positioning according to reperfusion treatment and recanalization status. The primary outcome is the ordinal distribution of modified Rankin Scale scores at 90 days after randomization. Blinded assessors will evaluate functional outcomes, and a blinded central imaging core laboratory will adjudicate imaging outcomes. Among participants with anterior-circulation large-vessel occlusion who undergo endovascular therapy, eligible and consenting participants may additionally enter an embedded randomized substudy evaluating selective intra-arterial infusion of 4 °C isotonic saline during thrombectomy.

Atrial fibrillation (AF) is associated with serious complications, including embolic strokes, heart failure, and mortality. Disruption of normal blood flow in the atrium, particularly in the context of an endocardium predisposed to thrombosis, increases the risk of thrombus formation. Once dislodged from the atrial cavity and traveling to the cerebral arteries, these thrombi can cause a cardioembolic stroke. The main risk factors for atrial cardiomyopathy (ACM) and AF are metabolic syndrome and aging. ACM is a condition that is difficult to diagnose because it is not clearly defined, except through histological analysis. Guided by the results of our experimental approaches, the investigators aim to address this challenge by examining ACM through the lens of one of its complications: cardioembolic stroke. BDNF (Brain-Derived Neurotrophic Factor) is a neurotrophic factor involved in inflammatory and metabolic processes that may play a key role in the development of these complications. This study explores the association between circulating levels of BDNF and the morphological and metabolic characteristics of ACM, as assessed by cardiac and brain imaging studies

Patients presenting with mild symptoms of acute ischemic stroke are common and account for approximately half of all acute ischemic stroke. About 30% of patients with minor stroke have a 90-day functional disability. Radiologically proven a large vessel occlusion (LVO) in patients with minor stroke is a well-established predictor of poor outcomes, while the poor outcomes following best medical management in patients with minor stroke with the underlying presence of a LVO are mainly driven by the occurrence of early neurological deterioration (END). Considering the well-known strong association between lack of arterial recanalization and END, endovascular therapy (EVT) appears as an attractive option to improve functional outcomes for LVO-related patients with stroke with mild symptoms. Whether EVT is safe and effective in patients with mild stroke with an LVO is currently debated, since these patients were typically excluded from the pivotal EVT trials. The current study aimed to further test the hypothesis that endovascular therapy would be superior to medical management with respect to functional recovery among low NIHSS patients caused by acute large-vessel occlusion in the anterior circulation.

This is a single-center, prospective, randomized, sham-controlled pilot clinical study designed to evaluate the efficacy, safety, and feasibility of early non-invasive electroencephalography-based brain-computer interface (EEG-BCI) rehabilitation training in patients with acute ischemic stroke. Eligible participants are adults aged 18 to 80 years with acute ischemic stroke, unilateral upper extremity motor impairment on the dominant-hand side, a baseline Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score of 10 to 50, and confirmed clinical stability 48 to 72 hours after stroke onset. Participants will be randomly assigned in a 1:1 ratio to receive either real EEG-BCI training plus standard early rehabilitation or sham BCI training plus standard early rehabilitation. Both groups will receive 10 days of training, with two sessions per day and approximately 30 minutes per session. The primary outcome is the change in FMA-UE score from baseline to 30 days after randomization. Secondary outcomes include changes in FMA-UE, Action Research Arm Test (ARAT), National Institutes of Health Stroke Scale (NIHSS), Modified Barthel Index (MBI), and modified Rankin Scale (mRS). Safety outcomes include symptomatic intracranial hemorrhage, any intracranial hemorrhage, neurological deterioration, seizures, falls, cardiovascular events, and training-related adverse events. This pilot study aims to provide preliminary evidence regarding the feasibility, safety, and potential efficacy of early EEG-BCI rehabilitation after acute ischemic stroke and to inform the design of future multicenter randomized controlled trials.

This study looks at whether stroke patients who take FXa inhibitors (a type of blood thinner) can safely receive clot-busting treatment (IVT). IVT is a common emergency treatment for stroke, but current guidelines say it should not be given to people who have taken FXa inhibitors in the last 48 hours. This is because doctors worry that IVT might cause dangerous bleeding in the brain. However, new research suggests that IVT might be safe for these patients. Some studies even show that stroke patients on FXa inhibitors who receive IVT do not have a higher risk of brain bleeding than other stroke patients. But because these studies were not designed as full medical trials, doctors still avoid IVT for this group. The SIFT trial will compare two groups of stroke patients who take FXa inhibitors: One group will receive IVT to see if it helps them recover better. One group will not receive IVT, which is the current standard. Doctors will check if IVT helps with recovery and if it causes any serious bleeding. If IVT is found to be safe and effective, this study could change stroke treatment guidelines and help more patients get life-saving care. Right now, some guidelines say that stroke patients on FXa inhibitors should have a blood test before getting IVT, to measure how much of the drug is in their system. But these tests are not available in most hospitals, and waiting for results could delay important treatment. The SIFT trial will not require this test before giving IVT. More and more people use FXa inhibitors to prevent strokes, but right now, they are being denied IVT based on old rules. If this study proves that IVT is safe for them, it could help doctors give better care to thousands of stroke patients.

This study will develop and validate a novel, active/conductive combined head and neck cooling system to selectively cool the ischemic penumbra during the acute phase of stroke, reducing neuronal damage and improving stroke outcomes. It complements existing reperfusion therapies offering a scalable neuroprotective option which will have wider implications across diverse healthcare settings. PHASE I: Technology Development \& Test Bench Optimization (Years 1-2) PHASE II: Validation in healthy volunteers (Year 3) PHASE III: Pilot, multicenter, randomized controlled (Phase 2a) trial (Year 4-5):

Stroke is the second leading cause of death worldwide, and ischemic stroke is the most frequent type. Intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 hours of symptom onset is the most effective therapy for patients with acute ischemic stroke. However, ischemic stroke progression and early reocclusion are not an uncommon phenomenon in patients after intravenous thrombolysis, resulting in neurological deterioration, which is associated with unfavorable functional outcomes. The underlying mechanism mainly involves the augmented platelet activation, triggered by the activated coagulation cascade during thrombolysis, which peaks within 2 hours of initiating rt-PA administration. Therefore, early antiplatelet therapy following intravenous thrombolysis represents a promising therapeutic approach to prevent neurological deterioration and improve the functional outcome of patients treated with intravenous thrombolysis. Currently, guidelines recommend initiating antiplatelet therapy 24 hours after intravenous thrombolysis due to the potential risk of increased bleeding. The safety and efficacy of early antiplatelet treatment following intravenous thrombolysis in patients with acute ischemic stroke remain clear. The study aims to test the hypothesis that in patients with acute ischemic stroke treated with intravenous thrombolysis, early administration of oral aspirin will improve functional outcomes without increasing the risk of intracranial hemorrhage.

Acute ischemic stroke is a leading cause of disability and mortality among dults in China. Although intravenous thrombolysis serves as first-line reperfusion therapy, nearly half of patients fail to achieve vascular recanalization. The reocclusion rate ranges from 14% to 34%, and many patients are left with residual neurological deficits. Early antiplatelet therapy initiated after thrombolysis may sustain persistent reperfusion and improve prognosis. However, current guidelines generally recommend delaying antiplatelet treatment until 24 hours post-thrombolysis due to bleeding risks, and direct evidence for the optimal initiation timing remains lacking. Tirofiban is a rapidly acting, short-half-life, reversible glycoprotein IIb/IIIa receptor antagonist. Previous studies indicate its potential benefits and acceptable safety when administered after intravenous thrombolysis. This is a multicenter, three-arm, open-label, endpoint-blinded randomized controlled trial. A total of 1482 non-cardioembolic patients without large or medium vessel occlusion and with residual neurological deficits (NIHSS ≥4) after thrombolysis will be enrolled. Participants will be randomly allocated to the tirofiban 24-hour group, tirofiban 48-hour group, or blank control group. The primary outcome is the proportion of patients with excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 90 days. Symptomatic intracranial hemorrhage and neurological outcomes will also be evaluated. The study aims to determine the optimal duration of tirofiban treatment after thrombolysis and provide high-level evidence for precise interventions in the acute phase of stroke.

The goal of this multicenter prospective observational study, conducted at 24 hospitals in Japan, is to learn about recurrent ischemic stroke in people with active cancer who develop acute ischemic stroke. One of the main objectives is to evaluate how often ischemic stroke recurs during follow-up. The main questions this study aims to answer are: * How often does ischemic stroke recur within 3 months after the initial stroke? * Which clinical factors may be associated with recurrent ischemic stroke? * What other clinical outcomes occur during follow-up? Participants will receive medical care determined by their treating physicians. Researchers will collect information about participants' cancer, stroke characteristics, test results, treatments, recurrent ischemic stroke, and other clinical outcomes. Researchers will also explore whether clinical factors are associated with recurrent ischemic stroke and other outcomes. This study will not assign participants to a specific treatment.

The goal of this study is to evaluate the safety and efficacy of JX10 versus placebo in participants with Acute Ischemic Stroke (AIS) who present for care within 4.5 to 24 hours. The main question the study aims to answer are: 1. JX10 improves functional outcomes as measured by the modified Rankin Scale score when compared with placebo following AIS. 2. Risk of symptomatic intracranial hemorrhage of JX10 in participants with AIS. During Part 1, participants will be randomized to JX 10 (1mg/kg, 3 mg/kg) or placebo. During Part 2, participants will receive JX10 (optimal dose chosen from Part 1) or placebo.

The research focuses on "post-market active surveillance and health economic evaluation of non-pharmacological therapies and innovative cerebrovascular diagnostic and therapeutic devices". Partnering with top-tier domestic institutions including the National Medical Administration Center, Regional Drug Evaluation Center, Beijing Tiantan Hospital, Capital Medical University, The First Affiliated Hospital of Naval Medical University, The First Affiliated Hospital of Harbin Medical University, and the School of Public Health, Fudan University, the project intends to: Establish standards for post-market active surveillance of cerebrovascular diagnostic and therapeutic devices and develop an intelligent surveillance system; Build a nationwide collaborative network covering multi-level medical institutions, and conduct serial cohort studies on cerebrovascular diseases based on the surveillance platform; Carry out safety, effectiveness and health economic evaluations for cerebrovascular diagnostic and therapeutic devices using data collected from the network and platform, so as to provide scientific evidence for the full-life-cycle regulation of such devices.

Endovascular thrombectomy (EVT) improves outcomes in acute ischemic stroke caused by large vessel occlusion. Despite successful recanalization, early neurological deterioration (END) remains frequent and is associated with poor outcomes. Transcranial Doppler (TCD) provides noninvasive, real-time assessment of cerebral blood flow velocities and may identify hemodynamic patterns associated with deterioration after EVT. PRECISE-TCD is a prospective, single-center observational study enrolling 180-300 patients undergoing EVT for anterior circulation large vessel occlusion at a tertiary academic medical center. Serial TCD examinations are performed immediately after EVT, daily for 72 hours, and as close as possible to early neurological deterioration events or clinically indicated head CT within 72 hours. The primary outcome is the association between TCD-derived hemodynamic parameters and END within 72 hours. Secondary outcomes include NIHSS at 24 hours and discharge, discharge disposition, and modified Rankin Scale at 90 days.

Extensive research is being conducted in search of neuroprotective agents for possible use in the acute phase of stroke and agents that can be used for neurorepair in later stages of stroke. Several trials have been conducted and are in progress using different pharmacological agents, but none of the studies involve the stimulation of ETB receptors to treat cerebral ischemic stroke. Sovateltide (IRL-1620, PMZ-1620) has been effective in animal models of cerebral ischemic stroke. Its safety and tolerability have been demonstrated in a human phase I study with 7 subjects. Clinical phase II and III results indicate that sovateltide is a novel, first-in-class, highly effective drug candidate for treating cerebral ischemic stroke. Safety and significant efficacy in improving the National Institutes of Health Stroke Scale (NIHSS), Modified Rankin scale (mRS), and Barthel index (BI) obtained in phase II and III studies in patients with cerebral ischemic stroke in India are convincing and encouraged us to investigate its safety and efficacy in cerebral ischemic stroke patients in the United States. Therefore, the plan is to conduct a phase III clinical study to evaluate the safety and efficacy of sovateltide therapy along with standard of care in patients of acute ischemic stroke.

The goal of this clinical trial is to learn if AB126, an investigational treatment made from neural exosomes, is safe and well tolerated when given to adults with moderate to severe acute ischemic stroke (AIS) who have undergone endovascular thrombectomy (EVT) but have had limited neurological improvement after the procedure. The study will also evaluate different doses of AB126 to help determine the highest dose that can be given safely. The main questions it aims to answer are: 1. Is AB126 safe and well tolerated when given to participants with AIS following EVT? 2. What dose of AB126 can be given safely? 3. Does treatment with AB126 provide preliminary evidence of improved neurological recovery following stroke? Researchers will compare participants who receive AB126 with participants who receive placebo to evaluate the safety and tolerability of AB126 and to collect preliminary information about recovery following stroke. Participants will: 1. Be randomly assigned to receive either AB126 or placebo. Neither participants nor the study team will know which treatment is assigned. 2. Receive 3 intravenous (IV) doses of AB126 or placebo. The first dose will be given as soon as possible after EVT, but no later than 6 hours after blood flow has been restored. The second and third doses will be given approximately 24 and 48 hours after EVT. 3. Undergo medical examinations, laboratory tests, neurological assessments, and brain imaging during the study. 4. Remain under observation at a comprehensive stroke center until hospital discharge. 5. Complete follow-up assessments by telephone and in person for approximately 1 year after treatment, including assessments at approximately 10, 30, 90, 180, 270, and 360 days after treatment.