Intra-arterial Selective Hypothermic Magnesium Sulfate Infusion in Combination With Endovascular Thrombectomy in Acute Ischemic Stroke (ICE-MAG)

Selective Intra-arterial Hypothermic Magnesium Sulfate Infusion in Combination With Endovascular Thrombectomy in Acute Ischemic Stroke: A Phase 1/2 Randomized Clinical Trial

The primary objective of this study is to estimate the safety and effectiveness of selective intra-arterial hypothermic magnesium sulfate infusion after endovascular thrombectomy in patients with acute ischemic stroke

Study Overview

• Status: Enrolling by invitation
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Procedure: Endovascular thrombectomy; Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (350 ml).; Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (500 ml).; Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (650 ml).

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Affiliated Hospital of Xuzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age range of 18-80 years old (including critical value);
2. No gender restrictions;
3. The clinical diagnosis is acute ischemic stroke of the anterior circulation, and the site of acute occlusion of the responsible vessel is located in the intracranial segment of the internal carotid artery and the M1 or M2 segment of the middle cerebral artery;
4. The symptoms and signs are consistent with acute anterior circulation ischemic stroke, NIHSS≥6;
5. The time from onset to endovascular thrombectomy of acute ischemic stroke is within 24 hours;
6. Indications for endovascular thrombectomy of acute ischemic stroke: ① ASPECTS score ≥ 6 points, within 6 hours of onset; ② 6-16 hours after onset, meeting DEFUSE-3 criteria (infarct core volume < 70 mL, mismatch rate ≥ 1.8 and mismatch volume > 15 mL) or DAWN criteria (NIHSS ≥ 10 and infarct core volume < 31 mL); Or NIHSS ≥ 20 and infarct volume 31-51 mL); ③ Within 16-24 hours of onset, meet DAWN criteria (NIHSS ≥ 10 points and infarct core volume < 31mL); Or NIHSS ≥ 20 points and infarct volume 31-51 mL)
7. The mRS score before stroke is 0-1 points;
8. Written informed consent provided by the patients or their legal relatives.

Exclusion Criteria:

General exclusion criteria:

1. Clinical manifestations suggest the presence of intracranial cerebral parenchymal hemorrhage or subarachnoid hemorrhage (even if imaging results are normal);
2. During a stroke, accompanied by epilepsy, an accurate NIHSS score cannot be obtained;
3. Accompanied by coma or mental disorders, it may interfere with the assessment of neurological function;
4. History of allergy to iodinated contrast agents or history of anaphylactic shock;

5. Baseline blood glucose<50mg/dL (2.78mmol) or>400mg/dL (22.20mmol);

   *Acceptable fingertip blood glucose results

6. Baseline platelet count<50 × 10^9/L;
7. Recently (i.e. within 30 days prior to inclusion in the study), there has been a history of significant gastrointestinal or other clinically significant bleeding; Active bleeding, abnormal coagulation factors, or bleeding tendency (taking anticoagulant drugs with INR ≥ 3 or PT ≥ 3 × ULN; if the researcher believes that the subject has no coagulation dysfunction, there is no need to wait for coagulation test results to determine whether to enroll);
8. During a stroke, there may be fever or active infections that require systemic treatment (such as active pulmonary tuberculosis);
9. History of chronic heart failure with NYHA criteria>1; Uncontrolled hypertension (systolic blood pressure>180mmHg or diastolic blood pressure>105mmHg after standardized treatment), hypotension (systolic blood pressure ≤ 100mmHg after standardized treatment), unstable angina, myocardial infarction, or bypass or stent surgery within 6 months;
10. Accompanied by pulmonary diseases such as chronic obstructive pulmonary disease, tuberculosis, pneumonia, pneumothorax, atelectasis, pulmonary fibrosis, bronchopulmonary dysplasia, pleural effusion, acute respiratory distress syndrome, irregular breathing, etc;
11. Severe liver and kidney dysfunction, including but not limited to: cirrhosis, hepatic encephalopathy, ascites, renal failure or uremia (Ccr<25ml/min), hepatorenal syndrome, etc;
12. Pregnant or lactating women;
13. Patients with acute stroke within 48 hours after percutaneous cardiovascular and cerebrovascular intervention and major surgery;
14. Currently participating in interventional clinical trials and using research drugs or medical devices;
15. Participants may not be able to complete this study due to other reasons or may not be considered eligible for inclusion by the researchers;

Image exclusion criteria:

1. CTA/MRA/DSA shows excessive vessel curvature, which may hinder the delivery of interventional instruments;
2. Suspected cerebral vasculitis based on medical history and CTA/MRA/DSA;
3. Suspected aortic dissection based on medical history and CTA/MRA/DSA;
4. CTA/MRA/DSA confirmed multi vessel regional occlusion (such as bilateral anterior circulation or anterior/posterior circulation, extracranial carotid artery with intracranial tandem lesions), or clinical evidence of bilateral infarction or multi regional infarction;
5. CTA/MRA/DSA confirms moyamoya disease or moyamoya syndrome;
6. CT/MRI confirms significant effect of midline shift;
7. CT/MRI confirms the presence of intracranial tumors (excluding small meningiomas);
8. CT/MRI confirms the presence of intracranial hemorrhage.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selective intra-arterial hypothermic magnesium sulfate infusion of low volume; Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (350 ml).	Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (350 ml).; According to patient's weight, magnesium sulfate (MgSO4) will be diluted to 350 ml 4°C saline solution (0.6μmol/kg/ml). During the thrombectomy procedure, a micro-catheter will be advanced until it reaches beyond the clot responsible for the ischemic symptoms, then cold 50 ml MgSO4 solution will be infused into the ischemic territory at 10 ml/min through the micro-catheter. After that, thrombectomy with a stent retriever will be performed to recanalize the occluded vessel as soon as possible. Immediately after successful thrombectomy, cold MgSO4 solution will be re-infused into the ischemic brain tissue through the catheter at a rate of 30 ml/min for 10 min.
Experimental: Selective intra-arterial hypothermic magnesium sulfate infusion of moderate volume; Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (500 ml).	Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (500 ml).; According to patient's weight, magnesium sulfate (MgSO4) will be diluted to 500 ml 4°C saline solution (0.6μmol/kg/ml). During the thrombectomy procedure, a micro-catheter will be advanced until it reaches beyond the clot responsible for the ischemic symptoms, then cold 50 ml MgSO4 solution will be infused into the ischemic territory at 10 ml/min through the micro-catheter. After that, thrombectomy with a stent retriever will be performed to recanalize the occluded vessel as soon as possible. Immediately after successful thrombectomy, cold MgSO4 solution will be re-infused into the ischemic brain tissue through the catheter at a rate of 30 ml/min for 10 min. Then pause for 5 min, followed by another 5 min of infusion at the original rate.
Experimental: Selective intra-arterial hypothermic magnesium sulfate infusion of high volumn; Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (650 ml).	Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (650 ml).; According to patient's weight, magnesium sulfate (MgSO4) will be diluted to 650 ml 4°C saline solution (0.6μmol/kg/ml). During the thrombectomy procedure, a micro-catheter will be advanced until it reaches beyond the clot responsible for the ischemic symptoms, then cold 50 ml MgSO4 solution will be infused into the ischemic territory at 10 ml/min through the micro-catheter. After that, thrombectomy with a stent retriever will be performed to recanalize the occluded vessel as soon as possible. Immediately after successful thrombectomy, cold MgSO4 solution will be re-infused into the ischemic brain tissue through the catheter at a rate of 30 ml/min for 10 min. Then pause for 5 min, followed by intermittent infusion at the original rate for another 5 min twice. The interval between two times is also 5 min.
Sham Comparator: Control; Endovascular thrombectomy alone	Procedure: Endovascular thrombectomy; Endovascular thrombectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at 90 days		90 days after intra-arterial hypothermic magnesium sulfate infusion
Effectiveness evaluation indicators:	Percentage of subjects with 90 days of functional independence (defined as mRS 0-2) (%) Evaluation time: 90 d (±14 d) after surgery	90 days after intra-arterial hypothermic magnesium sulfate infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 3-5 Treatment Emergent Adverse Event (TEAE) related to intervention occurring during treatment period	TEAE includes but not limited to cardiovascular system response, abnormal electrocardiogram, water-electrolyte imbalance, core temperature decreasing, vascular spasm, shiver, infect, disturbance of consciousness.	Within 72 hours after intra-arterial hypothermic magnesium sulfate infusion
All Treatment Emergent Adverse Event (TEAE) related to intervention occurring during treatment period		Within 72 hours after intra-arterial hypothermic magnesium sulfate infusion
All Treatment Emergent Adverse Event (TEAE) occurring during treatment period		Within 72 hours after intra-arterial hypothermic magnesium sulfate infusion
The proportion of symptomatic/asymptomatic intracranial hemorrhage within 24 hours		Within 24 hours after intra-arterial hypothermic magnesium sulfate infusion
No reflow rate	No reflow rate, defined as the percentage of subjects with a decrease in CBV or CBF by more than 15% compared to the contralateral side at 24 hours after treatment (%)	24 hours (±6 hours) after surgery
Cerebrospinal fluid parameters	The levels of Mg²⁺, glutamate, NFL, MMP-9, inflammatory factors, as well as the metabolomics/proteomics of cerebrospinal fluid, are used to verify the central nervous system protection mechanism	24 hours-7 day

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: August 27, 2025
• First Submitted That Met QC Criteria: September 1, 2025
• First Posted (Actual): September 9, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: magnesium sulfate; thrombectomy; intra-arterial hypothermic
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: ICE-MAG

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No