[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657710":3},{"organization":4,"outcomesModule":7,"designInfo":59,"detailedDescription":69,"studyPopulation":62,"armGroups":70,"interventions":83,"overallOfficials":62,"centralContacts":92,"locations":62,"responsibleParty":98,"collaborators":62,"id":100,"slug":101,"hasResults":102,"nctId":103,"briefTitle":104,"officialTitle":105,"acronym":106,"eligibilityCriteria":107,"healthyVolunteers":102,"sex":108,"minAge":109,"maxAge":62,"enrollmentInfo":110,"targetDuration":62,"studyType":113,"phases":114,"briefSummary":116,"conditions":117,"keywords":119,"overallStatus":123,"whyStopped":62,"lastUpdateSubmitDate":124,"lastUpdatePostDateStruct":125,"startDateStruct":128,"completionDateStruct":130,"leadSponsor":132,"locationsCount":62},{"fullName":5,"class":6},"Second Affiliated Hospital, Zhejiang University, School of Medicine","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":41},[9],{"measure":10,"description":11,"timeFrame":12},"Distribution of disability across the modified Rankin Scale at 90 days","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.","Day 90 after randomization",[14,17,20,23,27,31,35,38],{"measure":15,"description":16,"timeFrame":12},"Functional independence at 90 days","Proportion of participants with an mRS score of 0-2. The mRS ranges from 0 (no symptoms) to 6 (death); lower scores indicate better functional status.",{"measure":18,"description":19,"timeFrame":12},"Excellent functional outcome at 90 days","Proportion of participants with an mRS score of 0-1. The mRS ranges from 0 (no symptoms) to 6 (death); lower scores indicate better functional status.",{"measure":21,"description":22,"timeFrame":12},"All-cause mortality at 90 days","Proportion of participants who have died from any cause.",{"measure":24,"description":25,"timeFrame":26},"Change in National Institutes of Health Stroke Scale score from baseline to 24 hours","Change calculated as the 24-hour National Institutes of Health Stroke Scale (NIHSS) score minus the baseline score. The NIHSS ranges from 0 to 42; higher scores indicate greater neurological deficit, so a negative change indicates improvement.","Baseline and 24 hours after randomization",{"measure":28,"description":29,"timeFrame":30},"Change in National Institutes of Health Stroke Scale score from baseline to day 7 or discharge","Change calculated as the day-7\u002Fdischarge NIHSS score minus the baseline score. The NIHSS ranges from 0 to 42; higher scores indicate greater neurological deficit, so a negative change indicates improvement.","Baseline and Day 7 after randomization or hospital discharge, whichever occurs first",{"measure":32,"description":33,"timeFrame":34},"Early neurological improvement at 24 hours","Proportion of participants with a decrease of at least 4 points in NIHSS score from baseline or an NIHSS score of 0-1 at 24 hours. The NIHSS ranges from 0 to 42; lower scores indicate less neurological deficit.","24 hours after randomization",{"measure":36,"description":37,"timeFrame":34},"Early neurological deterioration at 24 hours","Proportion of participants with an increase of at least 4 points in NIHSS score from baseline that is not attributable to sedation. The NIHSS ranges from 0 to 42; higher scores indicate greater neurological deficit.",{"measure":39,"description":40,"timeFrame":34},"Successful reperfusion at the end of endovascular thrombectomy","Proportion of participants with final modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b, 2c, or 3, adjudicated from the final angiographic run. The mTICI scale ranges from 0 (no perfusion) to 3 (complete perfusion); higher grades indicate better reperfusion.",[42,46,49,53,56],{"measure":43,"description":44,"timeFrame":45},"Hemorrhagic transformation","Proportion of participants with any intracranial hemorrhage or hemorrhagic transformation classified according to the Heidelberg Bleeding Classification by the blinded central imaging core laboratory.","From randomization through Day 7",{"measure":47,"description":48,"timeFrame":45},"Symptomatic intracranial hemorrhage","Proportion of participants with symptomatic intracranial hemorrhage according to the Heidelberg Bleeding Classification, adjudicated using clinical deterioration and follow-up imaging.",{"measure":50,"description":51,"timeFrame":52},"Participants with any adverse event","Proportion of participants experiencing at least one adverse event after randomization. Events will be assessed for seriousness, severity, expectedness, and relationship to study intervention.","From randomization through Day 90",{"measure":54,"description":55,"timeFrame":52},"Participants with any serious adverse event","Proportion of participants experiencing at least one serious adverse event after randomization.",{"measure":57,"description":58,"timeFrame":52},"Participants with an intervention-related adverse event","Proportion of participants experiencing at least one adverse event considered related to a TOP component, including hypothermia, shivering, infection, serious arrhythmia, hemodynamic instability, vasospasm, vessel injury, fluid-overload concern, oxygen intolerance, carbon dioxide retention, respiratory deterioration, vomiting, aspiration, or intolerance of flat positioning.",{"allocation":60,"interventionModel":61,"interventionModelDescription":62,"primaryPurpose":63,"observationalModel":62,"timePerspective":62,"maskingInfo":64},"RANDOMIZED","PARALLEL",null,"TREATMENT",{"masking":65,"maskingDescription":66,"whoMasked":67},"SINGLE","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.",[68],"OUTCOMES_ASSESSOR","Reperfusion therapy with intravenous thrombolysis and\u002For 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.\n\nThe 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.\n\nTranscutaneous 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.\n\nProtocolized 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.\n\nHigh-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\u002Fmin 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.\n\nHead position will be dynamically adjusted according to reperfusion treatment and recanalization status. Participants receiving intravenous thrombolysis alone will initially be maintained in the 0° supine position when clinically feasible. Participants undergoing endovascular therapy will generally remain in the 0° supine position before completion of the procedure. After endovascular therapy, participants with successful reperfusion, defined as modified Thrombolysis in Cerebral Infarction grade 2b or higher, will be positioned with approximately 30° head elevation. In participants without successful reperfusion, a -20° Trendelenburg position may be used intermittently when clinically safe and tolerated. Positioning may be modified or discontinued for vomiting, aspiration risk, respiratory compromise, intracranial hemorrhage, cerebral edema, suspected intracranial hypertension, or other safety concerns.\n\nParticipants assigned to the control group will receive guideline-based reperfusion therapy and standard stroke-unit care. Clinically indicated oxygen therapy, antipyretic treatment, positioning changes, rescue therapy, and other necessary treatment will not be withheld.\n\nNeurological status will be assessed at baseline, approximately 24 hours after randomization, and at Day 7 or hospital discharge, whichever occurs first. Follow-up CT or MRI will generally be obtained at 24 to 36 hours after reperfusion treatment and again between Day 3 and Day 7. Functional outcome will be assessed at Day 90 by a trained evaluator blinded to treatment allocation.\n\nAmong participants with anterior-circulation large-vessel occlusion who undergo endovascular therapy, those who provide additional informed consent may enter an embedded randomized substudy of selective intra-arterial cooling. Participants in the substudy will undergo an independent 1:1 randomization to selective intra-arterial cooling or no selective intra-arterial cooling. When a microcatheter can cross the occlusion, 50 mL of 4 °C isotonic saline will be infused at 10 mL\u002Fmin before thrombectomy, followed by 300 mL at 30 mL\u002Fmin after the thrombectomy procedure. If pre-reperfusion infusion cannot be performed, 350 mL may be infused at 30 mL\u002Fmin after the endovascular procedure. The primary imaging outcome of the embedded substudy is final infarct volume assessed between Day 3 and Day 7 after reperfusion treatment, preferentially using the eligible scan closest to 72 hours.",[71,77],{"label":72,"type":73,"description":74,"interventionNames":75},"STOP Multimodal Neuroprotection Plus Standard Care","EXPERIMENTAL","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.",[76],"Other: Stimulation-Temperature-Oxygen-Positioning (STOP) Multimodal Neuroprotective Strategy",{"label":78,"type":79,"description":80,"interventionNames":81},"Standard Care Alone","ACTIVE_COMPARATOR","Participants receive guideline-based reperfusion therapy and standard stroke-unit care. Intravenous thrombolysis and\u002For 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.",[82],"Other: Guideline-Based Reperfusion Therapy and Standard Stroke-Unit Care",[84,88],{"type":6,"name":85,"description":86,"armGroupLabels":87,"otherNames":62},"Stimulation-Temperature-Oxygen-Positioning (STOP) Multimodal Neuroprotective Strategy","The STOP strategy comprises four protocolized nonpharmacological interventions added to guideline-based reperfusion therapy and stroke-unit care: (1) taVNS to the left auricular vagus nerve region (0.5 mA, 25 Hz, 200 μs, 20 min every 12 h for 5 days; first session as early as feasible and within 24 h after final reperfusion treatment); (2) temperature management targeting body temperature ≤37.5 °C through 72 h after final reperfusion treatment; (3) high-flow normobaric oxygen initiated as early as possible, preferably before or at reperfusion treatment, at 10 L\u002Fmin by reservoir mask in non-intubated patients or FiO2 1.0 in intubated patients, for 4 h; and (4) dynamic head positioning: 0° before reperfusion, 30° after mTICI ≥2b, and intermittent -20° Trendelenburg if mTICI \\\u003C2b when safe and tolerated. Components may be modified or stopped for safety and must not delay reperfusion therapy.",[72],{"type":6,"name":89,"description":90,"armGroupLabels":91,"otherNames":62},"Guideline-Based Reperfusion Therapy and Standard Stroke-Unit Care","Participants receive guideline-based reperfusion therapy, including intravenous thrombolysis and\u002For endovascular therapy when clinically indicated, together with standard stroke-unit care according to contemporary national and institutional guidelines. Standard care may include physiological monitoring and management, antithrombotic and lipid-lowering therapy, management of cerebral edema, dysphagia and aspiration precautions, venous thromboembolism prevention, rehabilitation, clinically indicated oxygen therapy, antipyretic treatment, positioning adjustments, and other rescue treatments. Clinically necessary treatment will not be withheld because of trial participation.",[78],[93],{"name":94,"role":95,"phone":96,"phoneExt":62,"email":97},"Shenqiang Yan, MD.","CONTACT","8613656694106","shenqiangyan@zju.edu.cn",{"type":99,"investigatorFullName":62,"investigatorTitle":62,"investigatorAffiliation":62,"oldNameTitle":62,"oldOrganization":62},"SPONSOR","100657710","stimulation-temperature-oxygen-positioning-multimodal-neuroprotection-for-acute-ischemic-stroke-stop-100657710",false,"NCT07840794","Stimulation-Temperature-Oxygen-Positioning Multimodal Neuroprotection for Acute Ischemic Stroke (STOP)","Stimulation-Temperature-Oxygen-Positioning (STOP) Multimodal Neuroprotective Strategy for Acute Ischemic Stroke Undergoing Reperfusion Therapy: A Multicenter Randomized Controlled Trial","STOP","Inclusion Criteria:\n\n* Age 18 years or older.\n* Clinical diagnosis of acute ischemic stroke.\n* Baseline National Institutes of Health Stroke Scale score of 5 to 25.\n* CTA, MRA, or DSA confirmation of an intracranial culprit arterial occlusion consistent with the presenting neurological deficit.\n* Eligible for guideline-recommended reperfusion therapy and planned to receive, or already initiated, intravenous thrombolysis and\u002For endovascular therapy.\n* Time from symptom onset or last known well to initiation of reperfusion therapy of 24 hours or less.\n* Pre-stroke modified Rankin Scale score of 0 or 1.\n* Written informed consent provided by the participant or an appropriate legally authorized representative.\n\nExclusion Criteria:\n\n* Intracranial hemorrhage on baseline imaging.\n* Established cerebral herniation, progressive severe cerebral edema, or an immediate requirement for decompressive surgery before enrollment.\n* 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.\n* Severe hypotension, shock, or other clinically significant hemodynamic instability.\n* Active persistent vomiting, inability to adequately protect the airway, severe respiratory distress, or another condition that makes protocolized 0° supine positioning unsafe.\n* Clinically significant bradycardia, atrioventricular block, severe arrhythmia, or another condition considered by the investigator to make transcutaneous auricular vagus nerve stimulation inappropriate.\n* Severe skin injury, infection, or another local condition at the auricular stimulation site that prevents transcutaneous auricular vagus nerve stimulation.\n* Severe systemic infection, sepsis, or another serious acute illness likely to substantially affect short-term prognosis.\n* Pregnancy or breastfeeding.\n* Severe progressive or terminal disease with expected survival of less than 3 months.\n* Current participation in another interventional clinical trial that may affect the assigned intervention or assessment of the primary outcome.\n* Any other condition that, in the investigator's judgment, makes trial participation inappropriate.","ALL","18 Years",{"count":111,"type":112},380,"ESTIMATED","INTERVENTIONAL",[115],"NA","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.\n\nA total of 380 adults with acute ischemic stroke treated with intravenous thrombolysis and\u002For 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.\n\nThe 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.\n\nThe 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.\n\nAmong 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.",[118],"Acute Ischemic Stroke",[120,121,122],"Endovascular thrombectomy","Large-vessel occlusion","Neuroprotection","NOT_YET_RECRUITING","2026-09-23",{"date":126,"type":127},"2026-09-25","ACTUAL",{"date":129,"type":112},"2026-11-01",{"date":131,"type":112},"2028-12-31",{"name":5,"class":6}]