Acute Ischemic Stroke
Conditions
Keywords
stroke, magnesium sulfate, neuroprotection
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.
Interventions
DRUGMagnesium sulfate
Following MT and IA injection of MgSO4, patients will also receive a continuous infusion of 16g MgSO4 diluted in 240 ml of 0.9% normal saline, infusing at a rate of 10 ml per hour for 24 hours.
Sponsors
Baylor College of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This trial will follow a dose escalation paradigm such that patients are sequentially enrolled into 4 groups. The first patients enrolled will be in the first group that receives the lowest dose. If the IA magnesium dose is safe in this group, the next patients will be enrolled in the 2nd group that receives a higher dose, this continuing until the final group.
Eligibility
Sex/Gender
ALL
Age
21 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
1. Patient with acute cerebral ischemia due to ICA or MCA occlusion 2. Major neurologic deficits: 6≤NIHSS≤20, 3. Premorbid mRS 0 or 1, or 2 4. Patient's clinical attending physician plans MT procedure as part of routine clinical care, 5. undergo MT with a TICI 2a or better recanalization, 6. Signed informed consent.
Exclusion criteria
1. Positive pregnancy test; 2. those undergoing MT with a TICI \<2a revascularization; 3. tandem occlusion of the cervical common or internal carotid artery; and 4. 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; 5. Second or third-degree heart block without a pacemaker in place, 6. Technical inability to navigate micro-catheter to target clot, 7. Patient already enrolled in another experimental treatment trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systemic MgSO4 Concentration | 6 hours post-MT, 24 hours post-MT | — |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Decrease 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 Inattention |
| Proportion of symptomatic intracranial hemorrhage (sICH) | 48 hours post-MT | sICH defined as 4 or more increase in NIHSS caused by hemorrhage |
| 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. |
| All causes of death after treatment | 48 hours post-MT, 90 days post-MT | — |
| Proportion of hemorrhagic transformation | 48 hours post-MT | — |
| 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. Dead |
Contacts
Primary ContactOmar Tanweer, MD
Outcome results
None listed