Magnesium And Verapamil After Recanalization in Ischemia of the Cerebrum: a Clinical and Translational Study.
Condition: Ischemic Stroke
MeSH terms: Ischemic Stroke; Ischemia
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase 1, blinded-outcome, randomized, placebo controlled study to investigate the
      safety and feasibility of super-selective intra-arterial administration of verapamil and
      magnesium sulfate immediately following successful endovascular thrombectomy as a potential
      neuroprotective synergistic therapeutic strategy in emergent large vessel occlusion stroke.
      This trial represents the first time that magnesium sulfate will be evaluated in human
      subjects as a superselectively administered neuroprotective agent administered in an acute
      time frame as an adjunct to intra-arterial thrombectomy. Furthermore, it will represent the
      first trial to evaluate combinational therapy for acute stroke neuroprotection.
    

Detailed description: 
      Participants will be recruited from patients evaluated at University of Kentucky Chandler
      Hospital for acute ischemic stroke. Participants with impaired capacity may be included, as
      the pathology to be studied (stroke) may impair their capacity. Initial contact will be made
      by the sub-investigators approved to obtain consent; all sub-investigators are practitioners
      who would make contact with potential participants in a clinical manner under standard
      clinical procedures. All sub-investigators will have access to stroke patients' medical
      information under normal circumstances. No special outreach is necessary to recruit
      particular populations. Enrollment goal will be 15 patients in each group.

      Participants will not be compensated or provided any incentives for study participation.

      The following describes all study procedures and evaluations that are to be done as part of
      the study.

      Visit 1-Baseline (Day 0):

        -  Obtain consent.

        -  Medical history taken from medical record, participant and family to determine
           eligibility based on inclusion/exclusion criteria (Standard of Care)

        -  Medication history (Standard of Care)

        -  Physical examination to include vital signs (Standard of Care)

        -  Pregnancy Testing (Standard of Care)

        -  NIH Stroke Scale (Standard of Care)

        -  Verify inclusion/exclusion criteria

        -  Randomization

        -  Cerebral angiogram with Endovascular Thrombectomy (Standard of Care)

        -  Study Drug administration

        -  Adverse event (AE) collection

      Immediately following the thrombectomy and study procedure all participants will be
      transferred to the Neuro-Intenstive care Unit (ICU) or other similar ICU for at least 24
      hours for monitoring and care. Vital signs and neurological assessments will be assessed
      every hour. Evaluations of the groin access site will be performed every every 15 minutes for
      the first hour, then 30 minutes for the second hour, and finally every hour for the next 4
      hours. Thereafter, groin site will be will performed at every shift.

      Visit 2 - Within 48 hours of admission

      • Non-contrast Postoperative MRI or CT (Standard of Care) The choice of one or the other will
      be determined by clinical criteria; CT or MRI may be preferable for different reasons
      depending upon the patient's clinical scenario.

      Visit 3 - ( By Discharge)

        -  NIH Stroke Scale (Standard of Care)

        -  Discharge Destination (Standard of Care)

        -  Cognitive Assessment (Standard of Care)

        -  Radiographic assessment of primary and secondary radiologic endpoints

      Visit 4 - End of Study (90 Days) (+/- 30 days)

        -  UBACC assessment will be used to assess consent capacity at follow-up.

        -  Montreal Cognitive Assessment (MoCA)

        -  Modified Rankin Score (mRS; Standard of Care)

      The visit may be conducted over the phone with the participant or their legally authorized
      representative.

      Unscheduled Visits. It is unexpected that Unscheduled Visits will be common, especially with
      the follow-up within 90 days after the procedure. However, subjects readmitted to the
      hospital for any reason will be tracked to determine if an AE occurred.

      Prohibited Medications, Treatments and Procedures: Participants on therapeutic
      anticoagulation will be excluded from the study. If medically necessary for underlying
      conditions, therapeutic anticoagulation may be started 72 hours the study drug
      administration.

      Participants should not use disopyramide within 48 hours before or 24 hours after verapamil
      and intravenous beta-block.

      Following successful completion of the baseline visit, participants will be randomized into
      the study. The randomization number will be assigned by the PI/neurointerventionalist.

      Participants will be randomized to receive 10mg of verapamil in 10 cc of normal saline and
      1000mg of magnesium sulfate in 20cc of normal saline or matching placebo.
    

Intervention name(s): Verapamil and Magnesium Sulfate; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Single dose strategy will be used; Single matching dosing strategy will be used
Other intervention name(s): 0.9% sodium chloride
Intervention MeSH terms: Magnesium Sulfate; Verapamil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment