Superselective Administration of VErapamil During Recanalization in Acute Ischemic Stroke "SAVER-I"

Active, not recruiting

Phase 1 Results N/A

Trial Description

The purpose of this study is to determine whether super-selective intra-arterial administration of verapamil immediately following successful intra-arterial thrombolysis is safe as a potential neuroprotective agent. Standard procedures are cerebral angiography and intra-arterial thrombolysis (intra-arterial administration of tPA and/or mechanical thrombectomy). Experimental procedure is superselective injection of verapamil intra-arterially.

Detailed Description

This trial represents the first time that verapamil will be evaluated in human subjects as a superselectively administered neuroprotective agent administered in an acute time frame as an adjunct to intra-arterial thrombolysis. The methods for administration, along with the routinized followup, will provide a paradigm for studying other potential neuroprotective agents. Subjects will undergo cerebral angiography with intra-arterial thrombolysis, which is standard of care. 'Intra-arterial thrombolysis will include possible intra-arterial administration of tPA, as well as possible mechanical thrombectomy with an accepted thrombectomy device. This includes the Mercí Retriever (Concentric Medical, Mountain View, CA), the Penumbra System (Penumbra, Alameda, CA), the Solitaire stent-triever (EV3, Covidien, Irvine, CA), and the Trevo stent-triever (Concentric Medical, Mountain View, CA). Immediately after the intra-arterial thrombolysis component of the angiographic procedure is completed, the microcatheter used during the procedure will be left in or guided into the vessel location of the clot. 10mg of verapamil in 20cc of normal saline will be administered over 20 minutes (1cc/minute) through the microcatheter and into the vessel previously obstructed by clot. At the conclusion of infusion, the microcatheter will be removed. Angiography through the guide catheter of the cerebral circulation in question will be performed to ensure no new thromboembolic event from the microcatheterization (standard of care). The catheters will be removed, and the arterial puncture site closed in the standard fashion. Patients will receive a noncontrast CT scan or MRI approximately 24 hours after intervention to determine the presence or absence of intracerebral hemorrhage (ICH) after intervention. This would be considered standard practice for intra-arterial thrombolysis. Both imaging studies can detect ICH, and 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. The determination of hemorrhage will be made by the official dictation of a diagnostic neuroradiologist not directly involved in the study. The hemorrhage will be considered an adverse event if it is deemed symptomatic in accordance with the criteria used in the International Management of Stroke (IMS) III study. Briefly, a hemorrhage is defined as symptomatic if occurring within 24+/-6 hours after study inclusion, temporally related to the intervention, and occurs with worsening neurological status as documented in the clinical exam. A 4 point or more increase in the NIHSS stroke scale would qualify as a significant worsening in status. Furthermore, hemorrhage that requires intervention surgically or endovascularly would be deemed significant.

Conditions

Interventions

  • Verapamil Drug
    Other Names: Isoptin; Verelan; Verelan PM; Calan; Bosoptin; Calaptin; Covera-HS
    Intervention Desc: Super-selective intra-arterial administration of 10mg verapamil in 20cc of normal saline will be administered over 20 minutes (1cc/minute) through the microcatheter and into the vessel previously obstructed by clot, immediately following successful intra-arterial thrombolysis. Half-life is 2.8-7.4 hrs.
    ARM 1: Kind: Experimental
    Label: Verapamil
    Description: Super-selective intra-arterial administration of 10 mg verapamil immediately following successful intra-arterial thrombolysis

Trial Design

  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Single Group Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary The primary endpoint will be the presence or absence of intracranial hemorrhage 24-48 hours after treatment Yes
Secondary Absence of intracranial hemorrhage At follow-up intervals: Day 30 ± 14 days, 3 Months ± 30 days, 6 Months ± 30 days, 12 Months± 30 days Yes

Sponsors