Stimulation-Temperature-Oxygen-Positioning (STOP) Multimodal Neuroprotective Strategy for Acute Ischemic Stroke Undergoing Reperfusion Therapy: A Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 380
- 主要终点
- Distribution of disability across the modified Rankin Scale at 90 days
研究概览
简要总结
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.
详细描述
Reperfusion therapy with intravenous thrombolysis and/or endovascular treatment is the cornerstone of acute ischemic stroke treatment. However, restoration of large-vessel blood flow does not necessarily result in complete tissue recovery. Persistent ischemic injury, microcirculatory dysfunction, neuroinflammation, blood-brain barrier disruption, cerebral edema, and hemorrhagic transformation may contribute to neurological injury before and after reperfusion.
The STOP strategy integrates four nonpharmacological neuroprotective interventions targeting complementary mechanisms. Participants assigned to the STOP group will receive transcutaneous auricular vagus nerve stimulation, protocolized temperature management, high-flow normobaric oxygen, and dynamic head positioning in addition to guideline-based reperfusion therapy and stroke-unit care. All trial interventions must be implemented without delaying intravenous thrombolysis, endovascular therapy, transfer, anesthesia, or other clinically indicated emergency treatment.
Transcutaneous auricular vagus nerve stimulation will be applied to the left auricular region innervated by the auricular branch of the vagus nerve. Recommended stimulation parameters are 0.5 mA current intensity, 25 Hz frequency, and 200 μs pulse width for 20 minutes every 12 hours for 5 days, for a planned total of 10 sessions. The first stimulation will be initiated as early as feasible after randomization and no later than 24 hours after completion of the final reperfusion treatment.
Protocolized temperature management will target a body temperature of 37.5 °C or lower through 72 hours after completion of the final reperfusion treatment. Antipyretic medication, physical cooling, cooling blankets, ice packs, infection assessment, and other clinically appropriate measures may be used when necessary.
High-flow normobaric oxygen will be initiated as early as possible, preferably before or at initiation of reperfusion treatment, without delaying reperfusion therapy. Non-intubated participants will receive oxygen at approximately 10 L/min through a reservoir mask or equivalent high-concentration oxygen delivery device. Intubated or mechanically ventilated participants will receive an inspired oxygen fraction of 1.0, with adjustment permitted for safety. Protocolized high-flow oxygen will continue for a total of 4 hours.
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
Treating clinicians and participants cannot be masked because the interventions are visible and procedural. Ninety-day modified Rankin Scale assessors will be trained, will not participate in acute treatment, and will remain unaware of treatment allocation. De-identified imaging will be adjudicated by a central core laboratory blinded to treatment assignment and clinical outcomes.
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 older.
- •Clinical diagnosis of acute ischemic stroke.
- •Baseline National Institutes of Health Stroke Scale score of 5 to
- •CTA, MRA, or DSA confirmation of an intracranial culprit arterial occlusion consistent with the presenting neurological deficit.
- •Eligible for guideline-recommended reperfusion therapy and planned to receive, or already initiated, intravenous thrombolysis and/or endovascular therapy.
- •Time from symptom onset or last known well to initiation of reperfusion therapy of 24 hours or less.
- •Pre-stroke modified Rankin Scale score of 0 or
- •Written informed consent provided by the participant or an appropriate legally authorized representative.
排除标准
- •Intracranial hemorrhage on baseline imaging.
- •Established cerebral herniation, progressive severe cerebral edema, or an immediate requirement for decompressive surgery before enrollment.
- •Severe hypoxemia, severe respiratory failure, or another clinical condition requiring continuous high-concentration oxygen therapy or specialized respiratory support that prevents implementation of the assigned oxygen protocol. Endotracheal intubation or mechanical ventilation alone is not an exclusion criterion.
- •Severe hypotension, shock, or other clinically significant hemodynamic instability.
- •Active persistent vomiting, inability to adequately protect the airway, severe respiratory distress, or another condition that makes protocolized 0° supine positioning unsafe.
- •Clinically significant bradycardia, atrioventricular block, severe arrhythmia, or another condition considered by the investigator to make transcutaneous auricular vagus nerve stimulation inappropriate.
- •Severe skin injury, infection, or another local condition at the auricular stimulation site that prevents transcutaneous auricular vagus nerve stimulation.
- •Severe systemic infection, sepsis, or another serious acute illness likely to substantially affect short-term prognosis.
- •Pregnancy or breastfeeding.
- •Severe progressive or terminal disease with expected survival of less than 3 months.
- •Current participation in another interventional clinical trial that may affect the assigned intervention or assessment of the primary outcome.
- •Any other condition that, in the investigator's judgment, makes trial participation inappropriate.
研究组 & 干预措施
STOP Multimodal Neuroprotection Plus Standard Care
Participants receive the protocolized STOP multimodal neuroprotective strategy in addition to guideline-based reperfusion therapy and stroke-unit care. The STOP strategy comprises transcutaneous auricular vagus nerve stimulation, protocolized normothermia, high-flow normobaric oxygen, and dynamic head positioning. Each component may be modified, interrupted, or discontinued for prespecified safety reasons. Trial procedures must not delay reperfusion therapy or other clinically necessary treatment.
干预措施: Stimulation-Temperature-Oxygen-Positioning (STOP) Multimodal Neuroprotective Strategy (Other)
Standard Care Alone
Participants receive guideline-based reperfusion therapy and standard stroke-unit care. Intravenous thrombolysis and/or endovascular therapy are performed according to contemporaneous national and institutional standards. Oxygen therapy, antipyretic treatment, positioning changes, and other rescue treatments are provided when clinically indicated, but no protocolized STOP bundle is mandated.
干预措施: Guideline-Based Reperfusion Therapy and Standard Stroke-Unit Care (Other)
结局指标
主要结局
Distribution of disability across the modified Rankin Scale at 90 days
时间窗: Day 90 after randomization
The modified Rankin Scale (mRS) is a 7-category global disability scale ranging from 0 (no symptoms) to 6 (death); lower scores indicate better functional status. The full ordinal distribution will be assessed by a trained evaluator blinded to treatment allocation.
次要结局
- All-cause mortality at 90 days(Day 90 after randomization)
- Functional independence at 90 days(Day 90 after randomization)
- Excellent functional outcome at 90 days(Day 90 after randomization)
- Change in National Institutes of Health Stroke Scale score from baseline to 24 hours(Baseline and 24 hours after randomization)
- Change in National Institutes of Health Stroke Scale score from baseline to day 7 or discharge(Baseline and Day 7 after randomization or hospital discharge, whichever occurs first)
- Early neurological improvement at 24 hours(24 hours after randomization)
- Early neurological deterioration at 24 hours(24 hours after randomization)
- Successful reperfusion at the end of endovascular thrombectomy(24 hours after randomization)