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

NCT07163299 | Enrolling By Invitation Phase 1 DMC

• 1 other identifier: ICE-MAG
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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. Addendum regarding phase 1 dosing implementation and planned phase 2 design: This integrated phase 1/2 trial originally planned weight-individualized magnesium perfusate calculated as Target Mg (μmol/mL) = 0.6 × patient body weight. During phase 1 recruitment, no dedicated emergency pharmacy fast-track compound workflow existed for urgent EVT procedures, which would cause reperfusion delay if individualized mixing was performed intraoperatively. Therefore, a uniform fixed magnesium concentration of 20.29 mmol/L was adopted as a temporary operational solution for all 9 phase 1 participants, with dose escalation only performed by increasing total infusion volume (350/500/650 mL). For the upcoming phase 2 cohort, we will retain the fully safe 650 mL maximum infusion volume and conduct independent magnesium concentration escalation across six ascending tiers: 20.29, 22.54, 25.36, 28.98, 33.81, and 40.57 mmol/L. These concentrations are prepared by diluting the standard 5 g magnesium stock into 1000 mL, 900 mL, 800 mL, 700 mL, 600 mL, and 500 mL pre-cooled normal saline respectively. After defining the maximum tolerated magnesium concentration tier, the original weight-tailored compounding formula will be fully implemented for subsequent efficacy cohorts. All protocol adjustments have received institutional review board amendment approval.

Conditions

Acute Ischemic Stroke

Keywords

thrombectomy; magnesium sulfate; intra-arterial hypothermic

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Grade 3-5 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) 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

  24 hours (±6 hours) after surgery

Study Arms (5)

Selective intra-arterial hypothermic magnesium sulfate infusion of low volume

EXPERIMENTAL

Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (350 ml). Note: In phase 1, all participants in these three volume-escalation arms received a uniform fixed-concentration perfusate of 20.29 mmol/L (5 g magnesium sulfate stock diluted into 1000 mL pre-cooled saline). Weight-tailored perfusate originally specified in registry could not be implemented due to absence of emergency pharmacy fast-track compounding workflow.

Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (350 ml).

Selective intra-arterial hypothermic magnesium sulfate infusion of moderate volume

EXPERIMENTAL

Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (500 ml). Note: In phase 1, all participants in these three volume-escalation arms received a uniform fixed-concentration perfusate of 20.29 mmol/L (5 g magnesium sulfate stock diluted into 1000 mL pre-cooled saline). Weight-tailored perfusate originally specified in registry could not be implemented due to absence of emergency pharmacy fast-track compounding workflow.

Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (500 ml).

Selective intra-arterial hypothermic magnesium sulfate infusion of high volumn

EXPERIMENTAL

Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (650 ml). Note: In phase 1, all participants in these three volume-escalation arms received a uniform fixed-concentration perfusate of 20.29 mmol/L (5 g magnesium sulfate stock diluted into 1000 mL pre-cooled saline). Weight-tailored perfusate originally specified in registry could not be implemented due to absence of emergency pharmacy fast-track compounding workflow.

Procedure: Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (650 ml).

Control

SHAM COMPARATOR

Endovascular thrombectomy alone

Procedure: Endovascular thrombectomy

Phase 2 Fixed-Volume Concentration-Escalation Cohort

EXPERIMENTAL

Intra-arterial selective cooling magnesium sulfate perfusate. All subjects receive a fixed maximum total infusion volume of 650 mL. Six ascending magnesium concentration tiers will be tested sequentially: 20.29 mmol/L, 22.54 mmol/L, 25.36 mmol/L, 28.98 mmol/L, 33.81 mmol/L, and 40.57 mmol/L. Each concentration is prepared by diluting one 5 g/10 mL magnesium sulfate heptahydrate stock vial into 1000 mL, 900 mL, 800 mL, 700 mL, 600 mL, or 500 mL pre-cooled 4 °C normal saline, respectively. After identifying the maximum tolerated magnesium concentration, the original registry-specified weight-individualized compounding formula will be implemented for subsequent efficacy-focused cohorts. This phase is not yet enrolling participants.

Procedure: Phase 2 Fixed-Volume Concentration-Escalation Cohort

Interventions

Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (500 ml). PROCEDURE

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.Note: The pre-planned weight-tailored magnesium solution could not be prepared intraoperatively in phase 1 due to unavailable emergency pharmacy workflow. All 9 patients received uniform 20.29 mmol/L perfusate, with only infusion volume escalated.

Selective intra-arterial hypothermic magnesium sulfate infusion of moderate volume

Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (650 ml). PROCEDURE

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.Note: The pre-planned weight-tailored magnesium solution could not be prepared intraoperatively in phase 1.All 9 patients received uniform 20.29 mmol/L perfusate.

Selective intra-arterial hypothermic magnesium sulfate infusion of high volumn

Endovascular thrombectomy PROCEDURE

Endovascular thrombectomy

Control

Endovascular thrombectomy combination with selective intra-arterial hypothermic magnesium sulfate infusion (350 ml). PROCEDURE

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. Note: The pre-planned weight-tailored magnesium solution could not be prepared intraoperatively in phase 1 due to unavailable emergency pharmacy workflow. All 9 patients received uniform 20.29 mmol/L perfusate, with only infusion volume escalated.

Selective intra-arterial hypothermic magnesium sulfate infusion of low volume

Phase 2 Fixed-Volume Concentration-Escalation Cohort PROCEDURE

This unenrolled phase 2 cohort uses a fixed 650 mL maximum infusion volume with six ascending magnesium concentrations: 20.29, 22.54, 25.36, 28.98, 33.81, 40.57 mmol/L. Each tier is mixed by diluting one 5 g magnesium stock into 1000/900/800/700/600/500 mL pre-cooled saline. After confirming safe magnesium levels, we will adopt the registry's weight-based formulation. Infusion protocols match phase 1, and this two-stage design is approved under IRB amendment No.XYFY2025-KL360-02

Phase 2 Fixed-Volume Concentration-Escalation Cohort

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range of 18-80 years old (including critical value);
• No gender restrictions;
• 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;
• The symptoms and signs are consistent with acute anterior circulation ischemic stroke, NIHSS≥6;
• The time from onset to endovascular thrombectomy of acute ischemic stroke is within 24 hours;
• 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)
• The mRS score before stroke is 0-1 points;
• Written informed consent provided by the patients or their legal relatives.

You may not qualify if:

• Clinical manifestations suggest the presence of intracranial cerebral parenchymal hemorrhage or subarachnoid hemorrhage (even if imaging results are normal);
• During a stroke, accompanied by epilepsy, an accurate NIHSS score cannot be obtained;
• Accompanied by coma or mental disorders, it may interfere with the assessment of neurological function;
• History of allergy to iodinated contrast agents or history of anaphylactic shock;
• Baseline blood glucose\<50mg/dL (2.78mmol) or\>400mg/dL (22.20mmol);
• \*Acceptable fingertip blood glucose results
• Baseline platelet count\<50 × 10\^9/L;
• During a stroke, there may be fever or active infections that require systemic treatment (such as active pulmonary tuberculosis);
• 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;
• 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;
• Severe liver and kidney dysfunction, including but not limited to: cirrhosis, hepatic encephalopathy, ascites, renal failure or uremia (Ccr\<25ml/min), hepatorenal syndrome, etc;
• Pregnant or lactating women;
• Patients with acute stroke within 48 hours after percutaneous cardiovascular and cerebrovascular intervention and major surgery;
• Currently participating in interventional clinical trials and using research drugs or medical devices;
• CTA/MRA/DSA shows excessive vessel curvature, which may hinder the delivery of interventional instruments;

Sponsors & Collaborators

• Capital Medical University: lead
• The Affiliated Hospital of Xuzhou Medical University: collaborator

Study Sites (1)

Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

Location

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology, Xuanwu Hospital, Capital Medical University

Model Details: This study was divided into two parts. The first part was a dose escalation study (non-randomized) using a "3+3" design. The second part was a randomized, parallel, open-label, endpoint-blinded study conducted at the maximum tolerated dose (MTD)

Study Record Dates

• First Submitted: August 27, 2025
• First Posted: September 9, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: August 13, 2026

Record last verified: 2026-08

Locations

CN (1)