Feasibility Study of IV Recombinant Tissue Plasminogen Activator (rtPA) vs. Primary Endovascular Therapy for Acute Ischemic Stroke (EARLY)

Endovascular Arterial Reperfusion vs. Intravenous ThromboLYsis for Acute Ischemic Stroke (EARLY): A Randomized Pilot Study of Ultra-early (<2 Hours) and Early (2-4.5 Hours) Reperfusion Therapy

This pilot trial will be the first step toward direct comparison of delivery of endovascular reperfusion therapy to intravenous recombinant tissue plasminogen activator (rt-PA) in a time-to-treatment framework shown as most effective by the NINDS rt-PA Stroke Trial. A randomized trial is justified for the following reasons: 1) The high rate of death and disability associated with ischemic stroke despite treatment with intravenous rt-PA mandates critical analysis of alternate therapies with therapeutic potential, 2) endovascular treatment for acute ischemic stroke is expanding in North America without compelling evidence of safety and efficacy from well-designed clinical trials, 3) critical cost-effectiveness analysis cannot be done without acquiring pertinent outcomes data from controlled studies.

Study Overview

• Status: Terminated
• Conditions: Stroke; Ischemic Stroke
• Intervention / Treatment: Drug: Intravenous Thrombolysis; Device: Endovascular Arterial Reperfusion

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Definite or probable ischemic stroke
• CT angiographic (CTA) evidence of intracranial vascular occlusion (internal carotid, middle cerebral - M1 or M2 divisions, anterior cerebral, posterior cerebral, or basilar artery) within 3.5 hours of symptom onset
• Able to receive assigned treatment within 4.5 hours of symptom onset
• Written informed consent from patient or surrogate, if unable to provide consent

Exclusion Criteria:

• CT evidence of early infarction in >1/3 of middle cerebral artery distribution
• Blood pressure > 185/110 mmHg refractory to anti-hypertensive therapy
• History of intracranial hemorrhage
• History of ischemic stroke within past 3 months
• History of major surgical procedure within past 14 days
• Gastrointestinal or genitourinary bleeding within past 14 days
• Glucose <50 or >400mg/dL
• Platelet count <100,000
• International normalized ratio (INR) ≥ 1.7
• Known history of bleeding diathesis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Intravenous Thrombolysis; 0.9mg/kg intravenous rt-PA (max dose 90mg) - 10% administered as a bolus over 1 minute and the remainder infused over 60 minutes.	Drug: Intravenous Thrombolysis; Other Names: Altelplase, rtPA
ACTIVE_COMPARATOR: Endovascular Arterial Reperfusion; Therapeutic options will include mechanical thrombectomy/clot disruption (Penumbra aspiration system, Solitaire device, and/or Reflex catheter) and/or intracranial stent deployment.	Device: Endovascular Arterial Reperfusion; Other Names: Penumbra, Solitaire

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recanalization Rate of Primary Intracranial Occlusion	The degree of recanalization (none, partial, complete) will be assessed in a blinded fashion on the 24-hour computed tomographic angiogram (CTA).	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Score on Modified Rankin Scale at 90 Days	Functional outcome at 90-days will be assessed with the modified Rankin Scale (mRS). The Modified Rankin Scale was completed by the physician; it is a 7 point scale rating any limitations in the study subject's social role. The scale ranges from 0 (no symptoms/disability) to 6 (death).	90 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Kevin M Barrett, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: June 1, 2013
• First Submitted That Met QC Criteria: June 1, 2013
• First Posted (ESTIMATE): June 5, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 5, 2016
• Last Update Submitted That Met QC Criteria: August 12, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: 12-002496

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO