Selective Intra-arterial Cooling Infusion With Endovascular Thrombectomy for Acute Ischemic Stroke: a Multicenter, Randomized, Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 258
- 试验地点
- 16
- 主要终点
- Distribution of Modified Rankin scale
研究概览
简要总结
This is a multicenter, randomized, controlled, subject- and assessor-blinded clinical trial. The research objective is to evaluate the safety and efficacy of selective intra-arterial cooling infusion combined with endovascular therapy in the treatment of acute anterior circulation large vessel occlusion stroke. This trial aims to enroll 258 subjects. Patients assigned to the control group will receive best medical management (BMM) and endovascular therapy (EVT). Those in the selective intra-arterial cooling infusion group (IA-SCI group) will undergo selective intra-arterial cold saline infusion, in addition to BMM and EVT. Subjects will be interviewed face-to-face at randomization, 24±6 hours, 48±6 hours after randomization, 7±2 days/discharge. Telephone interviews/ face-to face interviews will be performed at 30±3 days and 90±7 days after randomization. The primary outcome is the distribution of Modified Rankin Score at 90±7days after randomization.
详细描述
Acute ischemic stroke (AIS) is the leading cause of death and disability in China. Randomized trials involving patients with acute stroke due to large-artery occlusion in the anterior circulation have shown a benefit of endovascular therapy (EVT). Although EVT achieves successful recanalization in over 80% of patients, only 46% of patients are functionally independent (mRS 0-2) after the intervention . Therefore, new ancillary therapeutic strategies are needed to further improve the clinical outcomes.
Therapeutic systemic hypothermia has been suggested to be one such potential approach offering a viable neuroprotective strategy. However, several adverse events associated with the systematic hypothermia treatment have been reported. Those offset the therapeutic benefits of systemic hypothermia. Selective intra-arterial cooling infusion (IA-SCI) targets precisely the ischemic brain tissue with the infusion of hypothermic solutions. This approach induces a state of mild hypothermia in the ischemic region without causing substantial drops in core body temperature, thereby minimizing the incidence of systemic side effects. Previous studies have shown that IA-SCI with cold saline combined with EVT in AIS is safe and feasible.
Hence, the investigators design a multicenter, randomized, controlled, subject- and assessor-blinded clinical trial. The objective of this trial is to further explore the safety and efficacy of selective intra-arterial cooling infusion combined with EVT in the treatment of acute anterior circulation large vessel occlusion stroke, and 258 subjects will be enrolled. Subjects assigned to the control group will receive best medical management (BMM) and endovascular therapy (EVT). Those in the selective intra-arterial cooling infusion group (IA-SCI group) will undergo selective intra-arterial cold saline infusion, in addition to BMM and EVT. Subjects will be interviewed face-to-face at randomization, 24±6 hours, 48±6 hours after randomization, 7±2 days/discharge. Telephone interviews/ face-to face interviews will be performed at 30±3 days and 90±7 days after randomization. The primary outcome is the distribution of Modified Rankin Score at 90±7days after randomization.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 and ≤
- •Clinical signs consistent with AIS-LVO in the anterior circulation (intracranial segment of internal carotid artery, M1 segment of middle cerebral artery (MCA) demonstrated by computed tomography angiography (CTA) / magnetic resonance angiography (MRA)/ digital subtraction angiography (DSA)).
- •National Institutes of Health Stroke Scale (NIHSS) score (at screening) ≥6 and ≤
- •Modified Rankin Scale (mRS) score ≤1 before stroke onset.
- •Arterial puncture performed within 24 hours of symptom onset or last known well (LKW).
- •Written informed consent obtained from the patients or legally authorized representatives.
- •For patients admitted to the hospital within 6 hours of symptom onset, an Alberta Stroke Program Early CT Score (ASPECTS) ≥6 is required. For those admitted between 6 and 24 hours, the neuroimaging criteria of the DAWN or DEFUSE-3 trials are applied.
排除标准
- •Baseline CT/MRI reveals the presence of acute infarction in multiple vascular territories.
- •CTA/MRA/DSA confirms the presence of arterial dissection.
- •Evidence of intracranial hemorrhage or hemorrhagic transformation before thrombectomy.
- •Known allergies or intolerances to antiplatelet agents, anticoagulants, iodinated contrast, or anesthetics.
- •Severe infection (e.g., sepsis) or multiple organ failure.
- •Known hereditary or acquired hemorrhagic diathesis; coagulation factor deficiency; recent oral anticoagulant therapy with international normalized ratio (INR)>
- •Exception: Time elapsed since the last use of a novel oral anticoagulant ≥48 hours plus a normal activated partial thromboplastin time (APTT).
- •Baseline platelet count <50 × 109/L.
- •Blood glucose concentration <50 mg/dL (2.7 mmol/L) or >400 mg/dL (22.2 mmol/L).
- •Refractory hypertension that is difficult to control by medication (persistent systolic blood pressure (BP) >185 mmHg or diastolic BP >110 mmHg).
- •Previous New York Heart Association (NYHA) functional classification >I.
- •Coronary artery stenosis >70% or history of coronary artery bypass grafting.
- •Undergoing hemodialysis or peritoneal dialysis; severe renal insufficiency with a glomerular filtration rate <30 mL/min or serum creatinine >220 mmol/L (2.5 mg/dL).
- •Known intracranial aneurysm or cerebral arteriovenous malformation.
- •Malignant brain tumor or central nervous system infection.
- •Pre-existing neurological or psychiatric diseases that could confound the neurological or functional evaluations (e.g., dementia or mental illness)
- •Pregnant or lactating at admission.
- •Anticipated life expectancy <6 months.
- •Current participation in another interventional drug or device study. For any other reasons, the responsible clinicians believe that the patient is not suitable for SI-AC.
研究组 & 干预措施
Control group
Subjects will receive best medical management (BMM) plus endovascular therapy (EVT) according to the clinical guidelines.
IA-SCI group
Subjects randomized to the IA-SCI group will receive selective intra-arterial cooling infusion plus BMM and EVT.
干预措施: Selective Intra-arterial Cooling Infusion (IA-SCI) (Procedure)
结局指标
主要结局
Distribution of Modified Rankin scale
时间窗: 90 ±7days
the distribution of Modified Rankin scale (mRS) \[ranging from 0 (normal) to 6 (death)\]
次要结局
- Percentage of functional independence (mRS scale 0-2)(90 ±7days)
- Percentage of favorable outcome (mRS scale 0-1)(90 ±7days)
- The changes of infarction volume(7±2 days/discharge)
- National Institute of Health stroke scale (NIHSS) score(7±2 days/discharge)
- Barthel Index score(7±2 days/discharge)
- Rapid neurologic improvement(24±12 hours)
- Changes in ipsilateral tympanic membrane temperature(during surgery.)
- Power spectral density (PSD) assessed by continuous electroencephalogram (EEG)(within 7±2 days/discharge)
- (delta+theta)/(alpha+beta) power ratio (DTABR) assessed by continuous electroencephalogram (EEG)(within 7±2 days/discharge)
- Delta/alpha power ratio (DAR) assessed by continuous electroencephalogram (EEG)(within 7±2 days/discharge)
- Brain symmetry index (BSI) assessed by continuous electroencephalogram (EEG)(within 7±2 days/discharge)
- Symptomatic intracranial hemorrhage(24±12 hours)
- Any intracranial hemorrhage(24±12 hours)
- Intracranial arterial vasospasm after IA-SCI that requires further therapeutic intervention.(during operation)
- Proportion of subjects with pulmonary, urinary tract infection and gastroenteritis(7±2 days/discharge)
- Proportion of subjects with coagulation abnormalities(24±12 hours)
- Proportion of subjects with electrolyte imbalance(24±12 hours)
- Changes in core temperature before and after intra-arterial cooling infusion in the IA-SCI group.(During operation)
- any death(90±7 days)
- other AE/SAE(90±7 days)
- Final infarction volume(7±2 days/discharge)
- Barthel Index score(90±7 days)
- Procedure-related complications(during operation)
研究者
Shen Li
Professor
Beijing Shijitan Hospital, Capital Medical University