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 citicoline 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 citicoline 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.
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
- Cerebral angiogram with Endovascular Thrombectomy (Standard of Care)
- Study Drug administration
- Adverse event (AE) collection
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.
There are no particular prohibited medications, treatments, or procedures for after administration of the study drug. However, therapeutic anticoagulation is a relative contraindication to thrombectomy. Patients on therapeutic anticoagulation will be excluded from the study.
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 citicoline in 10cc of normal saline or matching placebo.
Trial Stopped: Study put on clinical hold by FDA. Sponsor decided to no pursue the study.
- Placebo Biological
Intervention Desc: Single matching dosing strategy will be used. ARM 1: Kind: Experimental Label: Placebo Description: The control group will receive saline only.
- Verapamil and Citicoline Drug
Other Names: CDP-choline Intervention Desc: Single dosing strategy will be used. ARM 1: Kind: Experimental Label: Verapamil and Citicoline Description: 10mg of verapamil in 10 cc of normal saline and 1000mg of citicoline in 10cc of normal saline will be administered over 20 minutes (1cc/minute) through the microcatheter and into the vessel previously obstructed by clot to the treatment group
- Allocation: Randomized
- Masking: Single Blind (Outcomes Assessor)
- Purpose: Treatment
- Endpoint: Safety Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||Number of participants having no symptomatic intracranial hemorrhage||within 48 hours after treatment||Yes|
|Secondary||Number of participants who had no systemic side effects from verapamil and citicoline administration.||within 90 days||Yes|
- Justin Fraser Lead