A Multicentre, Prospective, Randomized, Open-label, Blinded Endpoint, Pilot Clinical Trial Evaluating Subcutaneous Semaglutide in Patients With Acute Ischaemic Stroke Due to Anterior Circulation Large Vessel Occlusion Treated With Endovascular Thrombectomy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 100
- 主要终点
- Vanguard phase: Feasibility - Recruitment
研究概览
简要总结
Endovascular thrombectomy (EVT) is a procedure that improves recovery for people who suffer from a stroke by removing blood clots from large blood vessels in the brain. However, even with this treatment, over half of the patients either pass away or are left with serious disabilities within three months. This is partly because, even in cases of a successful EVT, brain tissue damage continues to grow. Extent of brain damage is a major factor in how well a patient recovers. Studies in animals have shown that a drug called semaglutide might help protect the brain and improve recovery after a stroke. Semaglutide is currently used for the treatment of diabetes and obesity and is given as a weekly injection under the skin.
The investigators are hoping to test whether giving semaglutide to stroke patients undergoing EVT can improve their recovery. A very large study at many hospitals is needed to answer this question. The investigators are starting with a smaller study to gain information on whether it is possible to perform a larger definitive one, and if so, how best to plan for it. In this first step we will study 100 patients with stroke who are scheduled for EVT in approximately 10 stroke centers across Canada. These patients will be randomly divided (like flipping a coin) into two groups: one will receive weekly semaglutide injections for 12 weeks, while the other will not receive the drug. The investigators will track how many patients agree to participate, how many stay in the study, and how well they follow the treatment plan. The investigators will also monitor the patients' recovery, overall health, and any side effects from the treatment. These results will provide important information to plan our larger study with the goal of reducing death rates and long-term disability in stroke patients undergoing EVT.
详细描述
Background/Importance:
Endovascular thrombectomy (EVT) has substantially improved functional outcomes and decreased mortality in acute ischemic stroke patients with large vessel occlusions (LVOs). However, more than half of the patients die or have significant disability at 90 days after EVT. Studies suggest considerable infarct growth despite successful EVT and infarct volume predicts survival and functional outcome after EVT. There is an unmet need for interventions to reduce infarct growth and improve the functional outcomes of patients with an acute LVO who undergo EVT. Glucagon-Like Peptide-1 receptor agonists (GLP-1 RAs) have been suggested to decrease infarct growth and improve motor and sensory impairments in both diabetic and non-diabetic animal models of stroke. GLP-1 RAs also consistently decreased the risk of major adverse cardiovascular events (MACE), with the most profound effect in stroke prevention, in large-scale randomized clinical trials (RCTs) of patients with and without history of diabetes.
Research Aims:
The overall goal of this study is to test whether semaglutide can improve the functional outcomes of adults with acute ischemic stroke attributed to an intracranial LVO who are planned for treatment with EVT. We are performing a pilot trial to obtain the factual feasibility prerequisites essential for the planning, design, funding and execution of a subsequent main phase trial.
Methods:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or above on the date of randomization.
- •EVT for an LVO in the anterior circulation, defined as the intracranial segment of the internal carotid artery (ICA) and/or the M1 or proximal M2 segment of the middle cerebral artery (MCA).
- •National Institutes of Health Stroke Scale (NIHSS) ≥ 6 points at the time of randomization.
- •Pre-stroke modified Rankin Scale (mRS) 0 or
- •Ability to randomize within 6 hours from the end of EVT.
- •Capable of giving signed informed consent either independently, or by a legally authorized representative (LAR).
排除标准
- •Pregnancy or breast-feeding.
- •Renal insufficiency (creatinine clearance < 30mL/min).
- •Cirrhosis or severe hepatic dysfunction, characterized by jaundice, encephalopathy or coagulopathy.
- •History of pancreatitis in the year prior to randomization or evidence of acute pancreatitis on randomization.
- •Active sepsis on randomization.
- •Cancer, regionally advanced or metastatic, or for which treatment had been administered within 6 months from randomization, or hematological cancer that is not in complete remission.
- •Any terminal medical condition with life expectancy of less than 3 months.
- •Personal or family history of medullary thyroid carcinoma (MTC) or patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).
- •Body mass index (BMI) less than
- •Known hypersensitivity to GLP-1 RAs.
- •Active treatment with an GLP-1RA prior to randomization.
- •Refusal or inability to administer subcutaneous (SC) injections by the patient or a caregiver.
- •Close affiliation with the investigational site.
研究组 & 干预措施
No Intervention
No Intervention
Semaglutide
Semaglutide
干预措施: Semaglutide (Drug)
结局指标
主要结局
Vanguard phase: Feasibility - Recruitment
时间窗: From site activation until the end of recruitment (approximately 24 months)
Recruitment of approximately 6 patients per site per year at approximately 10 Canadian stroke centres
Full trial: Functional Independenc
时间窗: From randomization to day 90±14
Functional independence at 90±14 days from randomization defined as a modified Rankin Scale (mRS) score of 2 or less.
Feasibility - Recruitment
时间窗: From site activation until the end of recruitment (approximately 24 months)
Recruitment of approximately 6 patients per site per year at approximately 10 Canadian stroke centres
次要结局
- Feasibility - Medication Adherence(From randomization to day 90±14)
- Feasibility - Retention Rate(From randomization to day 90±14)
- Vanguard phase: Medication Adherence(From randomization to day 90±14)
- Vanguard phase: Retention Rate(From randomization to day 90±14)
- Full trial: Functional Independence(At 7 (±2) and 30 (±7) days)
- Full trial: Functional Outcome(At 7 (±2), 30 (±7) and 90 (±14) days.)
- Full trial: Early Neurological Recovery(At 36 (±12) hours.)
- Full trial: Quality of Life(At 90 (±14) days.)
- Full trial: Incident Cerebrovascular and Cardiovascular events(At 90 (±14) days.)
- Medication Adherence(From randomization to day 90±14)
- Retention Rate(From randomization to day 90±14)