Stimulation-Temperature-Oxygen-Positioning Multimodal Neuroprotection for Acute Ischemic Stroke (STOP)

NCT07840794 | Not Yet Recruiting DMC

• 1 other identifier: STOP-RCT
• Study Type: interventional
• Target: 380
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Acute Ischemic Stroke

Keywords

Endovascular thrombectomy; Large-vessel occlusion; Neuroprotection

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• Functional independence at 90 days

  Day 90 after randomization

• Excellent functional outcome at 90 days

  Day 90 after randomization

• All-cause mortality 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

Other Outcomes (5)

• Hemorrhagic transformation

  From randomization through Day 7

• Symptomatic intracranial hemorrhage

  From randomization through Day 7

• Participants with any adverse event

  From randomization through Day 90

Study Arms (2)

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.

Other: Stimulation-Temperature-Oxygen-Positioning (STOP) Multimodal Neuroprotective Strategy

Standard Care Alone

ACTIVE COMPARATOR

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.

Other: Guideline-Based Reperfusion Therapy and Standard Stroke-Unit Care

Interventions

Stimulation-Temperature-Oxygen-Positioning (STOP) Multimodal Neuroprotective Strategy OTHER

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/min 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 \<2b when safe and tolerated. Components may be modified or stopped for safety and must not delay reperfusion therapy.

STOP Multimodal Neuroprotection Plus Standard Care

Guideline-Based Reperfusion Therapy and Standard Stroke-Unit Care OTHER

Participants receive guideline-based reperfusion therapy, including intravenous thrombolysis and/or 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.

Standard Care Alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• Clinical diagnosis of acute ischemic stroke.
• Baseline National Institutes of Health Stroke Scale score of 5 to 25.
• 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 1.
• Written informed consent provided by the participant or an appropriate legally authorized representative.

You may not qualify if:

• Intracranial hemorrhage on baseline imaging.
• Established cerebral herniation, progressive severe cerebral edema, or an immediate requirement for decompressive surgery before enrollment.
• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, Zhejiang University, School of Medicine: lead

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Shenqiang Yan, MD.

CONTACT

8613656694106; shenqiangyan@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2026
• First Posted: September 25, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 25, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share