Superselective Administration of VErapamil During Recanalization in Acute Ischemic Stroke

Ischemic Stroke Clinical Trial

— SAVER-I  

Official title:

Super-Selective Intra-Arterial Administration of Verapamil for Neuroprotection After Intra-Arterial Thrombolysis for Acute Ischemic Stroke Phase I Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02235558
• Other study ID #: 12-0975-F1V
• Status: Completed
• Phase: Phase 1
• First received: September 7, 2014
• Last updated: January 19, 2017
• Start date: February 1, 2013
• Est. completion date: March 21, 2016

Study information

• Verified date: January 2017
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: March 21, 2016
• Est. primary completion date: March 21, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Patients 21-85 years old, male or female

2. Suspected acute ischemic stroke based on clinical and radiographic evidence as determined and documented by the Stroke Neurology team at University of Kentucky.

3. Patients must meet criteria for intra-arterial thrombolysis as determined and documented by Interventional Neuroradiology attending physician (JF or AA).

4. Patients must have an acute thromboembolus within an intracranial artery (internal carotid, anterior cerebral, middle cerebral, posterior cerebral, basilar, vertebral) which undergoes pharmacologic (tissue plasminogen activator - tPA) and/or mechanical (eg. Merci or Penumbra clot retrieval) thrombolysis.

5. Patients with impaired capacity may be included, as the pathology to be studied (stroke) may impair their capacity (please see attached required documentation regarding impaired capacity).

6. Patients must have a TICI 2A or better revascularization via intra-arterial thrombolysis.

For reference, the TICI Scale is defined below:

0 = No Perfusion

1. = Perfusion past the initial obstruction but limited distal branch filling with little or slow distal perfusion

2. A = Perfusion of less than 50% of the vascular distribution of the occluded artery

2B = Perfusion of 50% or greater (but not complete) of the vascular distribution of the occluded artery 3 = Full perfusion with filling of all distal branches

Exclusion Criteria:

1. Pregnant women (would not qualify for intra-arterial thrombolysis as standard of care).

2. Patients who undergo intra-arterial thrombolysis for acute stroke, in whom only TICI 0 or 1 revascularization is obtained.

3. Patients with occlusion of the cervical common or internal carotid artery will be excluded from the study.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Verapamil
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.

Locations

Country	Name	City	State
United States	University of Kentucky Deparment of Neurosurgery, UK Chandler Hospital	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Justin Fraser

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Absence of systemic side effects of verapamil administration	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.	24-48 hours
Primary	The primary endpoint will be the presence or absence of intracranial hemorrhage	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.	24-48 hours after treatment
Secondary	Absence of intracranial hemorrhage	Improved clinical outcomes at followup intervals as measured by the modified Rankin score.	At follow-up intervals: Day 30 ± 14 days, 3 Months ± 30 days, 6 Months ± 30 days, 12 Months± 30 days