IV vs. IA tPA (Activase) in Acute Ischemic Stroke With CTA Evidence of Major Vessel Occlusion

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Susan Wilson, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00624000
First received: February 14, 2008
Last updated: November 4, 2011
Last verified: November 2011
  Purpose

Stroke is the third leading cause of death in the United States, responsible for 158,488 deaths in 1998 (American Heart Association). Nationwide, each year, an estimated 600,000 to 750,000 people suffer a new or recurrent stroke. Cerebral infarction comprises 80% of all strokes and is the result of a complex series of cellular metabolic events that occur rapidly after interruption of blood flow to a region of the brain. The extent of the brain damage is dependent on the duration and severity of the cerebral ischemia. Acute thrombus formation or migration is the principal cause of blood flow interruption in at least 75% of cerebral infarctions. In several animal models of focal cerebral ischemia, restoration of cerebral blood flow within two to six hours after initial occlusion has been associated with smaller volumes of cerebral infarction and improved functional outcome. An effective way of dissolving the thrombus is by administration of recombinant tissue plasminogen activator or Activase (Alteplase, rt-PA), which promotes the proteolytic action of plasmin from plasminogen at the site of a clot. In this study, the drug, Activase, will be administered in subjects with acute ischemic stroke (AIS) intravenously (IV) or by local intra-arterial (IA) injection. The use of the intravenous administration within 3 hours of stroke symptom onset is FDA approved whereas the intra-arterial administration, despite evidence of potential benefit, is not currently FDA approved. Although not FDA approved, this study will evaluate the effectiveness of IA thrombolysis with Activase, used in AIS because of its higher rate of recanalization , potential expansion of the time window out to 6 hours, and lower doses of thrombolytic agent used compared with systemic or intravenous Activase. The study is designed to test the feasibility and provide preliminary safety data regarding the relative benefits and risks of IA Activase as compared to IV Activase when administered per the NINDS rt-PA stroke study protocol, i.e. randomized within 3 hours of onset of symptoms of ischemic stroke then treated within 3 hours in the IV Activase arm and within 4 hours in the IA Activase arm.


Condition Intervention
Ischemic Stroke
Drug: IV tpa (Alteplase) vs IA tpa (Alteplase)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: IV vs. IA tPA (Activase) in Acute Ischemic Stroke With CTA Evidence of Major Vessel Occlusion

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Feasibility of enrolling 12 subjects with major vessel occlusion within 1 year and random 1:1 assignment to treatment with IV (N=6) and IA (N=6) IA Activase using the following criteria: Time to clinical and radiological assessments [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Time to IA Activase treatment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Preliminary safety assessment: 24 hour symptomatic ICH [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Resources utilized and risk-benefit of IA Activase treatment. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 90-day efficacy outcome including NIHSS, modified Rankin Scale and Barthel's Index. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • 24-h recanalization (TIMI 2/3) on MRA or CTA [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Major extracranial bleed (defined under section 3.3.3) and asymptomatic intracranial hemorrhage. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: March 2004
Study Completion Date: December 2008
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
IA administration of Alteplace vs. IV administration of Alteplace
Drug: IV tpa (Alteplase) vs IA tpa (Alteplase)
Alteplase was administered Either IA or IV x 1
Active Comparator: 2
IA administration of Alteplase vs.IV administration of Alteplase
Drug: IV tpa (Alteplase) vs IA tpa (Alteplase)
Alteplase was administered Either IA or IV x 1

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:Subjects will be eligible if the following criteria are met:

  • Ability to provide written informed consent and comply with study assessments for the full duration of the study.
  • Age > 18 years
  • NIHSS ≥ 4 or isolated aphasia or isolated hemianopsia

Exclusion Criteria:

  • NIHSS >30
  • Coma
  • Rapidly improving symptoms
  • History of stroke in the last 6 weeks
  • Seizure at onset
  • Subarachnoid Hemorrhage (SAH ) or suspected SAH
  • Any history of Intracrannial Hemorrhage (ICH)
  • Neoplasm
  • Septic embolism
  • Surgery, biopsy, trauma or LP in last 30 days
  • Head trauma in the last 90 days
  • Bleeding diathesis, or INR >1.7 or PTT >1.5 times baseline or platelet <100K
  • SBP >180 or DBP ≥100 despite treatment with 3 doses of IV Labetalol (10-20 mg Q10")
  • Lacunar stroke syndrome
  • CT: Hemorrhage, tumor (except small meningioma), significant mass effect, midline shift, acute hypodensity or >1/3 MCA territory sulcal effacement
  • Radiological contrast hypersensitivity
  • Angiographic: Dissection, lack of access, lack of occlusion, or nonatherosclerotic arteriopathy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00624000

Locations
United States, North Carolina
University of North Carolina Stroke Center
Chapel Hill, North Carolina, United States, 27599-7025
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Genentech
Investigators
Principal Investigator: Souvik Sen, MD University of North Carolina
  More Information

No publications provided by University of North Carolina, Chapel Hill

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Susan Wilson, Sub-Investigator, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00624000     History of Changes
Other Study ID Numbers: BB-IND # 11364
Study First Received: February 14, 2008
Last Updated: November 4, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of North Carolina, Chapel Hill:
Ischemic Stroke

Additional relevant MeSH terms:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on August 20, 2014