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

NCT00624000 | Completed

• 1 other identifier: BB-IND # 11364
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ischemic Stroke

Keywords

Ischemic Stroke

Outcome Measures

Primary Outcomes (4)

• 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

  3 years

• Time to IA Activase treatment

  3 years

• Preliminary safety assessment: 24 hour symptomatic ICH

  3 years

• Resources utilized and risk-benefit of IA Activase treatment.

  3 years

Secondary Outcomes (3)

• 90-day efficacy outcome including NIHSS, modified Rankin Scale and Barthel's Index.

  3 years

• 24-h recanalization (TIMI 2/3) on MRA or CTA

  3 years

• Major extracranial bleed (defined under section 3.3.3) and asymptomatic intracranial hemorrhage.

  3 years

Study Arms (2)

1

EXPERIMENTAL

IA administration of Alteplace vs. IV administration of Alteplace

Drug: IV tpa (Alteplase) vs IA tpa (Alteplase)

2

ACTIVE COMPARATOR

IA administration of Alteplase vs.IV administration of Alteplase

Drug: IV tpa (Alteplase) vs IA tpa (Alteplase)

Interventions

IV tpa (Alteplase) vs IA tpa (Alteplase) DRUG

Alteplase was administered Either IA or IV x 1

1; 2

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of North Carolina Stroke Center

Chapel Hill, North Carolina, 27599-7025, United States

Location

Related Publications (1)

• Sen S, Huang DY, Akhavan O, Wilson S, Verro P, Solander S. IV vs. IA TPA in acute ischemic stroke with CT angiographic evidence of major vessel occlusion: a feasibility study. Neurocrit Care. 2009;11(1):76-81. doi: 10.1007/s12028-009-9204-1. Epub 2009 Mar 10.

  PMID: 19277904 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tetradecanoylphorbol Acetate; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phorbol Esters; Phorbols; Diterpenes; Terpenes; Hydrocarbons; Organic Chemicals; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Souvik Sen, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sub-Investigator

Study Record Dates

• First Submitted: February 14, 2008
• First Posted: February 26, 2008
• Study Start: March 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: December 1, 2008
• Last Updated: November 8, 2011

Record last verified: 2011-11

Locations

US (1)