Study of Tenecteplase (TNK) in Acute Ischemic Stroke (TNK-S2B)

February 26, 2015 updated by: E. Clarke Haley, University of Virginia

Phase 2B Study of Tenecteplase (TNK) in Acute Ischemic Stroke (TNK-S2B)

The purpose of this study is to determine which of 3 different doses of tenecteplase (TNK) is better for treating stroke patients and if TNK offers an advantage over currently available treatment with tissue plasminogen activator (tPA).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Stroke is the third leading cause of death and a leading cause of adult disability in the United States and worldwide. To date, the only scientifically-proven and FDA-approved treatment for acute stroke is the clot-busting drug, tissue plasminogen activator (tPA). A newer clot-busting drug, tenecteplase (TNK), has chemical properties that make it a potentially safer and more effective drug for treating stroke. Preliminary testing of TNK in patients with acute stroke has been encouraging enough to warrant further testing.

This study, TNK-S2B, will compare three different doses of TNK with standard tPA treatment in patients with acute stroke. Patients will be chosen randomly to receive either TNK or tPA. Neither the patient nor his/her doctor will know which medication the patient received until the study is completely finished.

The first part of the study will look at results of treatment in the first 24 hours to select the best dose of TNK to carry forward into a more detailed comparison with standard tPA treatment. After at least 100-150 pairs of the best dose of TNK and tPA patients have been enrolled, entry into the study will pause, and the outcomes at 3 months after stroke will be compared to see if the results of TNK treatment are sufficiently promising as an improvement over standard treatment to justify expanding the study to find a definitive answer.

The study, which will be conducted in at least 8 large medical centers, is expected to last about 3 years.

Study Type

Interventional

Enrollment (Actual)

112

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92103-8466
        • University of California at San Diego
    • Colorado
      • Englewood, Colorado, United States, 80113-2771
        • Colorado Neurological Institutes
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins-Bayview Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0316
        • University of Michigan
    • New York
      • New Hyde Park, New York, United States, 11040
        • Long Island Jewish Hospital
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10032
        • Columbia University, Statistical Analysis Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas at Houston
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Patients with at least a serious, measurable deficit on the NIH Stroke Scale in language (aphasia score > 1), motor power (arm or leg > 1), vision (best visual score > 2), or attention (attention score > 2). Thus eligible patients may have a minimum total score of 1 if the deficit is in language or motor power. There is no maximum score that is exclusionary; even patients with severe hemispheric or brainstem deficits will be eligible, as is current practice with intravenous rt-PA. Patients with all ischemic stroke types and in all vascular distributions are eligible.
  • Must arrive at participating hospital and treatment begun within 3 hours of the onset of symptoms. Patients awakening with new symptoms must use the time last observed to be normal and awake and the total time cannot exceed three hours prior to treatment as the time of onset.
  • Must be 18 years of age or older.

Exclusion Criteria:

  • Patients with a) minor stroke symptoms (e.g., sensory loss, ataxia, dysarthria, or facial weakness alone) or b) major symptoms which are rapidly improving by the time of treatment.
  • Patients for whom a complete NIH Stroke Score cannot be obtained (e.g., intubated patients or complete amputees).
  • Patients with evidence of intracranial hemorrhage on pretreatment CT scan.
  • Patients with a clinical presentation that suggests subarachnoid hemorrhage, even if the initial CT scan is normal.
  • Patients who are known or suspected to be pregnant.
  • Patients with a known bleeding diathesis or patients with a platelet count < 100,000. For patients who are taking oral Warfarin (Coumadin), the results of the pretreatment International Normalized Ratio (INR) must be available prior to treatment and must be
  • </= 1.4. Patients who have received heparin within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible. Patients who have received low molecular weight heparin or heparinoid within 24 hours are also excluded.
  • Patients with major surgery or serious trauma excluding head trauma within 14 days or serious head trauma within 3 months.
  • Patients with a history of gastrointestinal or urinary tract hemorrhage in the previous 21 days.
  • Patients with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days.
  • Patients who, on repeated measurement, have a systolic blood pressure > 185, or a diastolic blood pressure > 110 mmHg when treatment is to begin, or require aggressive treatment to reduce blood pressure to within these limits.
  • Patients with a history of stroke in the previous 3 months or have ever had an intracranial hemorrhage considered to put them at increased risk for intracranial hemorrhage.
  • Patients with a serious medical illness likely to interfere with treatment or treatment might adversely affect that illness.
  • Patients with abnormal blood glucose thought to account for the neurological deficit.
  • Patients with a clinical presentation consistent with acute myocardial infarction or patients with presentation suggesting post-myocardial infarction pericarditis.
  • Patients with a seizure at onset of stroke thought to be presenting with post-ictal paralysis mimicking stroke.
  • Patients with pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations.
  • Patients who have received any other investigational drug within 14 days.
  • Patients who have large areas (greater than one lobe) of obvious low density on the baseline CT scan will be presumed to have had ongoing cerebral ischemia for greater than 3 hours, and will, therefore, be excluded. Patients with subtle early signs of cerebral infarction (e.g., sulcal effacement, blurring of the grey-white junction, asymmetry of the basal ganglia, insular ribbon sign, and others) and the dense artery sign on baseline CT scan will be eligible. Similarly, evidence of previous remote cerebral infarction on baseline CT will not be exclusionary.
  • Patients for whom informed consent cannot be obtained.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
tenecteplase
Drug: tenecteplase
This study will compare 3 different doses of tenecteplase to tPA.
Other Names:
  • TNK
Active Comparator: 2
tissue plasminogen activator, tPA
Drug: tissue plasminogen activator, tPA
To date, tissue plasminogen activator (tPA) is the only scientifically-proven and FDA-approved treatment for acute stroke.
Other Names:
  • tPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional Handicap (Modified Rankin Score)
Time Frame: 3 months
The scale range is from 0 (perfect health without symptoms) to 6 (death). Percentage of participants with Modified Rankin Score >=4 are reported.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: E. Clarke Haley, Jr., M.D., Clinical Coordinating Center, Department of Neurology, University of Virginia Health System
  • Principal Investigator: John L. P. Thompson, Ph.D., Statistical Analysis Center, Department of Biostatistics, Mailman School of Public Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

November 10, 2005

First Submitted That Met QC Criteria

November 10, 2005

First Posted (Estimate)

November 11, 2005

Study Record Updates

Last Update Posted (Estimate)

March 17, 2015

Last Update Submitted That Met QC Criteria

February 26, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11231 (Registry Identifier: DAIDS-ES)
  • R01NS045170 (U.S. NIH Grant/Contract)
  • R01NS037666 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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