Effect of Tirzepatide on Functional Outcomes in Patients With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy: A Multicenter, Randomized, Controlled, Blinded Outcome Assessment Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 430
- 试验地点
- 1
- 主要终点
- The primary efficacy outcome: Proportion of patients achieving an excellent functional outcome
研究概览
简要总结
Acute ischemic stroke caused by blockage of a large artery in the brain is one of the leading causes of death and long-term disability worldwide. For patients with this type of stroke, endovascular thrombectomy (EVT), a procedure that removes the blood clot and restores blood flow to the brain, has become the standard treatment. However, even when blood flow is successfully restored, many patients continue to experience disability because of ongoing brain injury caused by inflammation, oxidative stress, and damage to brain cells after the stroke.
This study aims to evaluate whether tirzepatide, a medication that activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) pathways, can improve recovery in patients with acute ischemic stroke caused by large vessel occlusion who receive thrombectomy. Tirzepatide is currently approved for the treatment of conditions such as type 2 diabetes and obesity. Previous studies have shown that tirzepatide can improve blood sugar control, reduce body weight, and provide beneficial effects on cardiovascular health. Laboratory studies and early clinical evidence suggest that medications targeting GLP-1 and GIP pathways may also have protective effects on the brain by reducing inflammation, protecting brain cells, improving blood vessel function, and supporting recovery after stroke.
In this study, eligible patients with acute ischemic stroke caused by blockage of a major brain artery will be randomly assigned to receive either tirzepatide plus standard stroke care or standard stroke care alone. Participants will receive two subcutaneous injections of tirzepatide: the first dose before the thrombectomy procedure and the second dose 7 days after the procedure. The study will include multiple hospitals and will use independent assessment of outcomes to ensure reliable evaluation of treatment effects.
The primary purpose of this study is to determine whether early treatment with tirzepatide can improve functional recovery 90 days after stroke, measured by the patient's ability to perform daily activities and live independently. The study will also evaluate whether tirzepatide is safe in patients with acute ischemic stroke by monitoring adverse events, complications, and other clinical outcomes.
The findings from this study may provide important evidence for a new treatment approach to improve recovery after thrombectomy and reduce disability among patients with severe ischemic stroke.
详细描述
1.1 Stroke Burden Approximately 2.4 million new stroke cases occur annually in China, resulting in about 1.1 million deaths each year. More than 11 million people are currently living with stroke, and the incidence, prevalence, and mortality rates continue to rise, with an increasing trend toward younger age groups. Stroke has become the leading cause of death and disability in China, imposing a substantial burden on patients, families, and society as a whole.
Among all stroke subtypes, acute ischemic stroke (AIS) accounts for approximately 70%-80% of cases. Patients with concomitant large vessel occlusion (LVO) experience the most severe neurological deficits. Although some patients are eligible for intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA), only 26.5% achieved functional independence at 90 days, while the 90-day mortality rate remains as high as 18.9%, making AIS-LVO one of the greatest challenges in stroke management.
1.2 Endovascular thrombectomy in patients with large vessel occlusion The cornerstone of treatment for acute ischemic stroke with large vessel occlusion (AIS-LVO) is rapid recanalization of the occluded artery to salvage the ischemic penumbra. Since 2015, five landmark randomized controlled trials (RCTs), including MR CLEAN, EXTEND-IA, and SWIFT PRIME, published in The New England Journal of Medicine, have demonstrated the efficacy of endovascular thrombectomy (EVT) in patients with AIS-LVO, representing a revolutionary breakthrough in stroke care.
Subsequently, a pooled meta-analysis published in The Lancet in 2016 showed that EVT achieved a 90-day favorable functional outcome rate of 46.0%, representing a 2.71-fold increase compared with standard medical therapy, further confirming the substantial clinical benefit of thrombectomy.
The DAWN and DEFUSE 3 trials further extended the EVT treatment window to 24 hours after symptom onset. These studies demonstrated that, among carefully selected patients with salvageable ischemic penumbra identified by advanced imaging, EVT significantly improved clinical outcomes even when performed 6-24 hours after stroke onset. More recently, the BAOCHE and ATTENTION trials extended the proven benefits of EVT to posterior circulation stroke. Consequently, EVT has received the highest level of recommendation in international stroke guidelines.
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)
盲法说明
This study will employ a blinded-endpoint assessment design. Outcome measures, including 90-day mRS assessment, EQ-5D-5L questionnaire, neurological deficit evaluations during hospitalization, and imaging assessments, will be performed by trained investigators who are unaware of treatment allocation. Assessments will be conducted through either face-to-face visits or telephone follow-up.
入排标准
- 年龄范围
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria:
- •Age >18 years and ≤80 years;
- •Acute ischemic stroke with imaging-confirmed anterior large vessel occlusion at:
- •Terminal ICA,
- •M1 segment of the middle cerebral artery, or
- •Dominant M2 segment;
- •NIHSS score between 6 and 25 prior to randomization;
- •Alberta Stroke Program Early CT Score (ASPECTS) of 6-10 before randomization;
- •Time from symptom onset (or last known well) to planned endovascular thrombectomy within 24 hours;
- •Pre-stroke mRS score of 0-1;
- •Patients presenting within 6 hours of symptom onset are eligible for direct EVT. Patients presenting between 6 and 24 hours after symptom onset must undergo advanced imaging demonstrating a salvageable perfusion mismatch and meet the DEFUSE-3 criteria: an infarct core volume <70 mL, a mismatch volume >15 mL, and a mismatch ratio >1.8;
- •Written informed consent provided by the participant or a legally authorized representative.
排除标准
- •Participants meeting any of the following criteria will be excluded:
- •Posterior-circulation large vessel occlusion stroke;
- •Receipt of intravenous thrombolysis prior to randomization;
- •Simultaneous bilateral anterior-circulation occlusions or concurrent anterior- and posterior-circulation occlusions;
- •Intracranial hemorrhage on baseline CT or MRI, including subarachnoid hemorrhage or intracerebral hemorrhage; evidence of large established infarction, defined as:
- •ASPECTS <6,
- •Ischemic core volume ≥70 mL on CTP, or
- •Infarction involving >1/3 of the middle cerebral artery territory;
- •Active bleeding within the previous month (e.g., gastrointestinal, genitourinary, or retinal hemorrhage), major organ surgery or biopsy within 14 days before stroke onset, or known bleeding diathesis;
- •Refractory hypertension despite treatment, defined as persistent systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg;
- •Severe hepatic or renal impairment, including:
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²,
- •Serum creatinine >200 μmol/L,
- •Child-Pugh Class C or higher liver disease,
- •Recurrent unexplained hypoglycemia;
- •Blood glucose <2.7 mmol/L or >22.2 mmol/L; platelet count <80 × 10⁹/L; or international normalized ratio (INR) >1.7;
- •Previous use of GLP-1 receptor agonists or GIP receptor agonists, or known hypersensitivity to these agents;
- •Personal or family history of medullary thyroid carcinoma (MTC) or diagnosis of Multiple Endocrine Neoplasia Type 2 (MEN2);
- •History of severe anxiety or depression prior to stroke onset;
- •Severe underlying disease with life expectancy <1 year, such as advanced malignancy;
- •Pregnancy or breastfeeding;
- •Participation in another clinical trial.
研究组 & 干预措施
Tirzepatide Intervention Group
Participants will receive two subcutaneous injections of tirzepatide: the first administered before EVT and the second administered 7 days after EVT, in addition to standard medical care
干预措施: Tirzepatide (Drug)
结局指标
主要结局
The primary efficacy outcome: Proportion of patients achieving an excellent functional outcome
时间窗: 90 ± 7 days after randomization
A excellent functional outcome is defined as modified Rankin Scale (mRS) score of 0-1 at 90 days. The Modified Rankin Scale ranges from 0 to 6, where 0 indicates no symptoms, 1 indicates symptoms without significant disability, 2 indicates slight disability, 3 indicates moderate disability, 4 indicates moderately severe disability, 5 indicates severe disability, and 6 indicates death. Higher scores indicate worse functional outcomes.
The primary safety outcome: All-cause mortality
时间窗: 90 ± 7 days
death from any cause within 90 days
次要结局
- The secondary efficacy outcome: Distribution of mRS scores at 90 days after randomization(90 ± 7 days)
- The secondary efficacy outcome: Proportion of patients achieving an good functional outcome(90 ± 7 days)
- The secondary safety outcome: Symptomatic intracranial hemorrhage (sICH)(within 48 hours after thrombectomy)
研究者
yifang zhu
Professor
Second Affiliated Hospital of Soochow University