The Role of SGLT2 Inhibitors in Stroke-reperfusion Injury:A Multi-Center, Randomized, Open-Label, Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 150
- 主要终点
- Occurrence of malignant edema
研究概览
简要总结
Background:
Reperfusion therapies, including intravenous rt-PA and mechanical thrombectomy, significantly improve outcomes in acute ischemic stroke. However, these interventions also increase the risk of hemorrhagic transformation and malignant edema. Preclinical studies have demonstrated that Canagliflozin, an SGLT2 inhibitor, reduces astrocyte swelling and brain edema in a transient middle cerebral artery occlusion (tMCAo) model. While SGLT2 inhibitors have shown neuroprotective effects in the acute phase of ischemic stroke, their potential to mitigate hemorrhagic transformation and malignant edema following reperfusion therapy in humans remains unexamined.
Aims:
This study aims to evaluate the effect of SGLT2 inhibitors on hemorrhagic transformation and malignant edema in patients undergoing reperfusion therapy for acute ischemic stroke.
Methods:
This is a multi-center, randomized, open-label, controlled study enrolling ischemic stroke patients aged 18 years or older who meet predefined inclusion and exclusion criteria. Participants will be randomized to receive Canagliflozin 100 mg once daily for 14 days or no additional treatment before undergoing mechanical thrombectomy. Clinical data collection will include baseline demographics, medical and medication history, NIHSS scores at admission and 24 hours post-reperfusion, stroke subtype, modified Thrombolysis in Cerebral Infarction (TICI) scores, laboratory results, and modified Rankin Scale (mRS) scores at discharge and 3 months post-stroke.
The primary outcome is to assess the association between Canagliflozin use and the severity of hemorrhagic transformation and malignant edema. Hemorrhagic transformation will be classified using the Heidelberg criteria, and malignant edema will be defined as a midline shift of ≥5 mm. Brain imaging, including CT scans at 24 hours post-intervention and additional scans as clinically indicated, will be reviewed by blinded radiologists. Brain MRA will also be performed to assess infarct size and edema progression.
Importance:
This study aims to explore the potential for repurposing SGLT2 inhibitors as a therapeutic strategy in acute ischemic stroke. If Canagliflozin is shown to reduce hemorrhagic transformation and malignant edema, it could offer a novel adjunctive treatment to improve patient outcomes following reperfusion therapy.
详细描述
Clinical Study Protocol The Role of SGLT2 Inhibitors in Stroke-Reperfusion Injury: A Multi-Center, Randomized, Open-Label, Controlled Trial Version 6.0 | Date: 2024-12-10
1. Study Overview 1.1 Study Objectives Evaluate the efficacy of Canagliflozin 100 mg daily versus no treatment in reducing hemorrhagic transformation and malignant edema following reperfusion therapy in acute ischemic stroke.
1.2 Study Design
- Type: Multi-center, randomized, open-label, controlled trial
- Blinding: Open-label
- Randomization: Yes
- Design: Parallel-group
- Treatment Duration: 14 days
- Study Period: 3 years (2025-2027)
- Study Sites: Two medical centers in Taiwan
- Dose Adjustment: No 1.3 Endpoints
Primary Efficacy Endpoints:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Patients must have been diagnosed with acute ischemic stroke and large vessel occlusion by a neurologist, with confirmation supported by CT perfusion scans.
- •Patients must be scheduled to undergo mechanical thrombectomy.
排除标准
- •Patients with have stage 4 or 5 chronic kidney disease (estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m² on dialysis)
- •Patients with currently taking an SGLT2i or within 3 months prior to enrollment
- •Patients with a known hypersensitivity or allergic reaction to Canagliflozin
- •Patients with type 1 diabetes mellitus
- •Patients with pregnancy or lactation
研究组 & 干预措施
control group
Patients who are enrolled will be randomly assigned to either the control group.
Not receiving Canagliflozin before undergoing mechanical thrombectomy.
study group
Patients who are enrolled will be randomly assigned to either the study group. Receiving Canagliflozin 100mg QD before undergoing mechanical thrombectomy. The prescribed duration of Canagliflozin 100mg QD will be 14 days.
干预措施: Canagliflozin 100mg (Drug)
结局指标
主要结局
Occurrence of malignant edema
时间窗: On the 3rd to 5th day for MRI after EVT
Diagnosed if midline shift ≥5 mm on brain imaging or symptomatic brain swelling requiring decompressive craniectomy, leading to in-hospital death, or coma at discharge.
mRS at 3rd month after stroke onset
时间窗: 3 months after stroke onset
Assesses health-related quality of life using modified Rankin Scale (mRS) to assess disability level post-stroke for understanding the recovery situation of the patient.
Mortality rate at 3rd month after stroke onset
时间窗: After stroke onset in 3 months.
To understand if the patient is surviving or not after stroke onset.
次要结局
- Occurrence of hemorrhagic transformation(During hospitalization for 14 days)
- Occurrence f parenchymal hematoma type2(During hospitalization for 14 days)
- NIHSS 24 hours later(24 hours after EVT)
- mRS at discharge(Day 14 at hospital discharge)
- EQ-5D at 3rd month after stroke onset(3 months after stroke onset)
- infarct size on brain MRI(Day 1 after EVT)
- upregulation of arterial biomarkers (MMP-9) after EVT(Day 1 before EVT is executed and after EVT finished)
研究者
Po-Lin Chen
Director
Taichung Veterans General Hospital