Intra-arterial Hypothermic Magnesium Sulfate Infusion in Combination with Endovascular Thrombectomy in Acute Ischemic Stroke (Hypo-Mag)

Intra-arterial Hypothermic Magnesium Sulfate Infusion in Combination with Endovascular Thrombectomy in Acute Ischemic Stroke: a Safety Study

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

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Procedure: Intra-arterial hypothermic magnesium sulfate infusion; Procedure: Endovascular thrombectomy; Drug: Intravenous thrombolysis

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Xunming Ji, MD, PhD; Phone Number: 010-83198952; Email: jixm@ccmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital, Capital Medical University
      • Contact: Yang Zhang, MD; Phone Number: 010-83911991; Email: zy1192268729@163.com

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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intra-arterial hypothermic magnesium sulfate infusion; Patients will receive intra-arterial hypothermic magnesium sulfate infusion after endovascular thrombectomy.

Procedure: Intra-arterial hypothermic magnesium sulfate infusion; According to patient's weight, magnesium sulfate (MgSO4) will be diluted to 330 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 30 ml MgSO4 solution will be infused into the ischemic territory at 15 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.; Procedure: Endovascular thrombectomy; All patients that are eligible for endovascular thrombectomy will receive this surgery in aim to remove thrombus and restore reperfusion.; Drug: Intravenous thrombolysis; All patients that are eligible for Intravenous thrombolysis will receive 0.9mg/kg rt-PA in aim to remove thrombus and restore reperfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality at 90 days	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 h		Within 24 hours after intra-arterial hypothermic magnesium sulfate infusion

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): January 10, 2025
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: January 3, 2025
• First Submitted That Met QC Criteria: January 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Neuroprotection; Acute ischemic stroke; Magnesium sulfate; Endovascular Thrombectomy; Intra-arterial hypothermic infusion
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Body Temperature Changes; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia; Hypothermia; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Reproductive Control Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Anti-Arrhythmia Agents; Membrane Transport Modulators; Anticonvulsants; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: Hypo-Mag

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No