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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00252239
Recruitment Status : Terminated (Slow enrollment)
First Posted : November 11, 2005
Results First Posted : January 19, 2015
Last Update Posted : March 17, 2015
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
E. Clarke Haley, University of Virginia

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Stroke Drug: tenecteplase Drug: tissue plasminogen activator, tPA Phase 2

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  (Clinical Trial)
Actual Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 2B Study of Tenecteplase (TNK) in Acute Ischemic Stroke (TNK-S2B)
Study Start Date : November 2005
Actual Primary Completion Date : March 2009
Actual Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1
Drug: tenecteplase
This study will compare 3 different doses of tenecteplase to tPA.
Other Name: 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 Name: tPA

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00252239

United States, California
University of California at San Diego
San Diego, California, United States, 92103-8466
United States, Colorado
Colorado Neurological Institutes
Englewood, Colorado, United States, 80113-2771
United States, Maryland
Johns Hopkins-Bayview Medical Center
Baltimore, Maryland, United States, 21224
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-0316
United States, New York
Long Island Jewish Hospital
New Hyde Park, New York, United States, 11040
Mount Sinai Medical Center
New York, New York, United States, 10029
Columbia University, Statistical Analysis Center
New York, New York, United States, 10032
United States, Texas
University of Texas at Houston
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
National Institute of Neurological Disorders and Stroke (NINDS)
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 automatically indexed to this study by Identifier (NCT Number):
Responsible Party: E. Clarke Haley, Professor, Department of Neurology, University of Virginia Identifier: NCT00252239     History of Changes
Other Study ID Numbers: 11231
R01NS045170 ( U.S. NIH Grant/Contract )
R01NS037666 ( U.S. NIH Grant/Contract )
First Posted: November 11, 2005    Key Record Dates
Results First Posted: January 19, 2015
Last Update Posted: March 17, 2015
Last Verified: February 2015

Keywords provided by E. Clarke Haley, University of Virginia:
tissue plasminogen activator

Additional relevant MeSH terms:
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action