Intra-Arterial Magnesium Therapy After Mechanical Thrombectomy in Acute Ischemic Stroke
- Registration Number
- NCT06956521
- Lead Sponsor
- Baylor College of Medicine
- Brief Summary
The goal of this Phase I unblinded, dose-escalation trial is to evaluate the safety and tolerability of intra-arterial magnesium sulfate injection after mechanical thrombectomy in patients experiencing acute ischemic stroke. This trial is one of the first trials to look at IA administration of magnesium sulfate into at risk brain tissue in a selective and localized fashion.
- Detailed Description
Patients meeting inclusion and exclusion criteria will undergo a baseline neurologic assessment and will be enrolled following informed consent. The patient will then be taken to the Interventional Radiology suite where the patient will undergo MT as per the standard of care. Participation in this study will never delay the timely provision of urgent MT to patients.
Additionally, as part of the study procedure, the patient will be assigned to Treatment Group 1,2, 3 or 4 based on the consecutive sampling scheme. The first 6 patients enrolled will be in group 1 and receive the lowest dose of MgSO4 as described below. If the analysis of this group deems this dosage to be safe, the following patients will be enrolled into group 2. The same scheme will be followed until all 4 groups are enrolled.
Patients in all groups will receive IA MgSO4 as follows (investigational):
Patients in each group will receive the specified dose of MgSO4 (listed below) diluted in 0.9% sodium chloride. The infusion of IA MgSO4 will be administered over 1-2 minutes.
Dose Escalation Schedule Group 1 0.25g IA MgSO4 Group 2 0.5g IA MgSO4 Group 3 1g IA MgSO4 Group 4 1.5g IA MgSO4
Given the minimal safety data on IA MgSO4, this dosage regimen was derived from previous IV MgSO4 studies and a singular IA MgSO4 study in a separate population to cautiously investigate the safety and tolerability for IA MgSO4.
Following MT and IA infusion, patients will receive a continuous infusion of IV MgSO4 for 24 hours. The maintenance infusion will contain 16g of MgSO4 diluted in 240 ml of 0.9% normal saline, infused at a rate of 10 ml per hour for 24 hours. Patients will follow the standard of care monitoring for post-MT patients with the addition of monitoring for magnesium toxicity.
All pre and post imaging is standard of care for this procedure, including follow up MRI (or CT if MRI contraindicated).
Following discharge from the hospital, all patients enrolled in the study protocol will be followed up in the clinic at 3 months to evaluate the patient's functional clinical outcome. If for any reason, the patient cannot come back for a follow-up visit, the PI/Co-PI's will contact the patient via phone/email to gather the required data. A minimum of mRS and NIHSS should be gathered for follow-up data.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
- Patient with acute cerebral ischemia due to ICA or MCA occlusion
- Major neurologic deficits: 6≤NIHSS≤20,
- Premorbid mRS 0 or 1, or 2
- Patient's clinical attending physician plans MT procedure as part of routine clinical care,
- undergo MT with a TICI 2a or better recanalization,
- Signed informed consent.
- Positive pregnancy test;
- those undergoing MT with a TICI <2a revascularization;
- tandem occlusion of the cervical common or internal carotid artery; and
- subjects on therapeutic anticoagulation, as it is a relative contraindication to MT, and could be a confounding variable predisposing to intracranial hemorrhage including coagulation disorders, systematic hemorrhagic tendency, thrombocytopenia <80000/mm3;
- Second or third-degree heart block without a pacemaker in place,
- Technical inability to navigate micro-catheter to target clot,
- Patient already enrolled in another experimental treatment trial. Exclusion criteria 1-3 are all contraindications to magnesium therapy,
- mRS>2 caused by a history of prior stroke,
- Severe hepatic dysfunction, severe renal dysfunction (<30 mL/min), increase in ALT or AST (more than 2 times of upper limit of normal value), increase in serum creatinine (more than 1.5 times of upper limit of normal value) or requiring dialysis;
- Unsuitable for this clinical study assessed by researcher. Subjects will not be excluded if they received IV t-PA as standard of care.
- patient is on neuromuscular blocking agents including depolarizing (succinylcholine) and nondepolarizing subtypes (rocuronium, vecuronium, etc);
- patient is taking any form of CNS depressant including barbiturates, narcotics, outside the setting of anesthesia or ICU sedation
- patients taking digoxin or other cardiac glycoside
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 0.25g Magnesium Sulfate Magnesium sulfate 0.25g of magnesium sulfate (MgSO4) will be diluted in 0.9% sodium chloride for intra-arterial (IA) administration via the guide catheter already in place in the intracranial internal carotid artery (ICA) on the affected side for MT. The infusion will be administered over 1-2 minutes. 0.5g Magnesium Sulfate Magnesium sulfate 0.5g of magnesium sulfate (MgSO4) will be diluted in 0.9% sodium chloride for intra-arterial (IA) administration via the guide catheter already in place in the intracranial ICA on the affected side for MT. The infusion will be administered over 1-2 minutes. 1.0g Magnesium Sulfate Magnesium sulfate 1.0g of magnesium sulfate (MgSO4) will be diluted in 0.9% sodium chloride for intra-arterial (IA) administration via the guide catheter already in place in the intracranial ICA on the affected side for MT. The infusion will be administered over 1-2 minutes. 1.5g Magnesium Sulfate Magnesium sulfate 1.5g of magnesium sulfate (MgSO4) will be diluted in 0.9% sodium chloride for intra-arterial (IA) administration via the guide catheter already in place in the intracranial ICA on the affected side for MT. The infusion will be administered over 1-2 minutes.
- Primary Outcome Measures
Name Time Method Proportion of severe adverse events 48 hours post-MT severe adverse events including femoral artery dissection, local thrombosis, pseudoaneurysm, arteriovenous fistula, neurotoxicity and loss of reflexes due to magnesium, cardiovascular toxicity (arrythmias, severe bradycardia), respiratory depression
Systemic MgSO4 Concentration 6 hours post-MT, 24 hours post-MT
- Secondary Outcome Measures
Name Time Method Proportion of patients with Modified Rankin Scale (mRS) 0 to 2 90 days post-MT mRS is a measure of global disability. Total Scale range is 0-6, with lower values indicating better outcomes. mRS \</= 2 is considered functional independence based on modified Rankin score.
Modified Rankin Scales (mRS) 90 days post-MT mRS is a measure of global disability. Total Scale range is 0-6, with lower values indicating better outcomes.
0. No symptoms at all
1. No significant disability despite symptoms; able to carry out all usual duties and activities
2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
3. Moderate disability; requiring some help, but able to walk without assistance
4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention
6. DeadDecrease in National Institutes of Health Stroke Scale (NIHSS) 48 hours post-MT NIHSS is a measure of neurologic deficit. Total Score range 0-42, with higher scores indicating greater severity. The 11 domains assessed are:
1a-c Level of consciousness 2. Best Gaze 3. Visual 4. Facial Palsy 5a. Motor left arm 5b. Motor right arm 6a. Motor left leg 6b. Motor right leg 7. Limb Ataxia 8. Sensory 9. Best Language 10. Dysarthria 11. Extinction and InattentionProportion of symptomatic intracranial hemorrhage (sICH) 48 hours post-MT sICH defined as 4 or more increase in NIHSS caused by hemorrhage
Proportion of hemorrhagic transformation 48 hours post-MT All causes of death after treatment 48 hours post-MT, 90 days post-MT