TNK-tPA Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by University of Calgary
Sponsor:
Collaborators:
Vancouver General Hospital
Ottawa Hospital Research Institute
University of Alberta
Hopital Charles Lemoyne
Sunnybrook Research Institute
Kingston General Hospital
Information provided by (Responsible Party):
Dr. Michael Hill, University of Calgary
ClinicalTrials.gov Identifier:
NCT01654445
First received: July 25, 2012
Last updated: February 18, 2013
Last verified: February 2013
  Purpose

This trial will enroll patients that have been diagnosed with a transient ischemic attack (TIA) or minor stroke that has occurred within the past 12 hours. Anyone diagnosed with a minor stroke faces the possibility of long-term disability and even death, regardless of treatment. Stroke symptoms such as weakness, difficulty speaking and paralysis may improve or worsen over the hours or days immediately following a stroke. The purpose of this research trial is to study the effects of a clot-dissolving drug, tenecteplase (TNK-tPA), as a treatment for patients who arrive within twelve hours from stroke onset. This study is attempting to see if TNK-tPA given through a vein in the arm (intravenous) to patients is a safe treatment for stroke patients. Neither the safety nor the effectiveness of this treatment has been proven yet.

This trial will be conducted at several site in Canada.

Dr Michael Hill and Dr. Shelagh Coutts are the Principal Investigators of this trial, coordinated at the University of Calgary, Foothills Medical Centre.


Condition Intervention Phase
Ischemic Stroke
Drug: Tenecteplase
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Prospective, Two Cohort, Dose-escalation, Safety and Feasibility Study of Thrombolysis for Minor Ischemic Stroke With Proven Acute Symptomatic Occlusion Using TNK-tPA

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • Proportion of serious bleeding events [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: Yes ]
    The primary safety outcome will be the rate of expected serious adverse events associated with study drug. This will be defined as the number patients with at least one SAE divided by the number of patients enrolled by dose-tier. Thus, the unit of analysis will be the patient and not the SAE.


Secondary Outcome Measures:
  • NIHSS 0 and mRS 0 and Barthel Index > 90 [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Complete neurological and functional recovery at 30 days defined as: NIHSS 0 and mRS 0 iii)Complete neurological and functional recovery at 90 days defined as: a. NIHSS 0-1 and mRS 0-1 and Barthel Index > 90


Other Outcome Measures:
  • Recanalization on follow-up CTA 4-8 hours post-treatment [ Time Frame: 4-8 hours ] [ Designated as safety issue: No ]
    Recanalization defined on follow-up 4-8 hour CTA


Estimated Enrollment: 50
Study Start Date: July 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TNK-tPA Tenecteplase
This is an open-label trial, all patients will receive tenecteplase.
Drug: Tenecteplase
Tenecteplase will be given to the patient as an intravenous bolus over 1- 2 minutes within 90 minutes of the first slice of the CTA. This is an open-label trial, all patients will receive tenecteplase, either tier 1 or tier 2 dosage.
Other Name: TNK-tPA

Detailed Description:

The primary objective of TEMPO-1 is to demonstrate the safety and feasibility of using TNK-tPA (tenecteplase), a thrombolytic agent that is relatively novel to the treatment ischemic stroke but well-established in the treatment of myocardial infarction, to treat minor ischemic stroke patients with proven acute symptomatic occlusions. Up to 80% of ischemic stroke is minor and initially non-disabling. These patients present with a transient ischemic attack (TIA) or minor stroke.An overwhelming majority are not treated with thrombolysis as they are considered "too good to treat" by most physicians.

TEMPO-1 will enroll patients within a 12 hour time window with a NIHSS score of <6 and an ASPECTS >5. Patients must have an intracranial occlusion on CTA. Study drug must be administered within 90 minutes from the first slice of CTA. This is an open- label, multi-centre trial, dose- escalated trial. A total of 50 patients will be enrolled, 25 per tier. There will two dose tiers at 0.1 mg/kg and 0.25 mg/kg. Advancement to the second dose-tier will be dependent upon safe completion of the 1st dose tier and the approval of the DSMB.

Patients will undergo a study CT angiogram of the intracranial circulation between 4-8 hours after treatment to determine the biological effect of the drug - whether the occluded artery has recanalized or not. Patients will be assessed at 24 and 48 hours, and at Days 5, 30, and 90.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Acute ischemic stroke in an adult patient (18 years of age or older)
  2. Onset (last-seen-well) time to treatment time < 12 hours.
  3. Minor stroke defined as a baseline NIHSS < 6 at the time of randomization. Patients must have a demonstrable neurological deficit on physical neurological examination.
  4. Any acute intracranial occlusion (MCA, ACA, PCA, VB territories) defined by non-invasive acute imaging (CT angiography) that is neurologically relevant to the presenting symptoms and signs. An acute occlusion is defined as TICI 0 or TICI 1 flow.
  5. Pre-stroke independent functional status in activities of daily living with pre-stroke estimated modified Barthel Index of 90 or greater AND premorbid mRS 0 or 1.
  6. Informed consent from the patient or surrogate.
  7. Patients can be treated within 90 minutes of the CT/CTA being completed.

Exclusion Criteria:

  1. Hyperdensity on NCCT consistent with any intracranial hemorrhage. Any clinical suspicion of any intracranial hemorrhage even in the absence of visible blood on baseline brain imaging.
  2. Large acute stroke >1/3 MCA territory or ASPECTS<5 visible on baseline CT scan.
  3. Core of established infarction. No area of grey matter hypodensity at a similar or lesser density to white matter or in the judgment of the enrolling neurologist is consistent with a subacute ischemic stroke > 12 hours of age.
  4. Clinical history, past imaging and clinical judgment suggest that the intracranial occlusion is chronic.
  5. Patient is a candidate for and should receive standard of care IV tPA.
  6. Stroke occurring as an in-patient. An in-patient is a person who has been officially admitted to the hospital to a ward bed. A patient in the ED who has not been formally admitted is still considered to be an outpatient.
  7. Patient has a severe or fatal or disabling illness that will prevent improvement or follow-up or such that the treatment would not likely benefit the patient.
  8. Patient cannot complete follow-up due to co-morbid non-fatal illness or is visiting the host sites city and cannot return for follow-up.
  9. Pregnancy.
  10. Patient is actively taking dual antiplatelet medication (aspirin & clopidogrel) in the last 48 hours.
  11. International normalized ratio > 1.4
  12. Standard thrombolysis exclusions (Taken from Canadian guidelines1)
  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: NCT01654445

Contacts
Contact: Michael D Hill, MD 403-944-8065 michael.hill@ucalgary.ca
Contact: Shelagh B Coutts, MD 403-944-1594 scoutts@ucalgary.ca

Locations
Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Carol C Kenney, RN, CCRP    403-944-4286    Tempo1@ucalgary.ca   
Contact: Michelle R Wright    403-944-8065    Tempo1@ucalgary.ca   
Principal Investigator: Michael D Hill, MD, FRCPC         
Principal Investigator: Shelagh B Coutts, MD, FRCPC         
Sponsors and Collaborators
University of Calgary
Vancouver General Hospital
Ottawa Hospital Research Institute
University of Alberta
Hopital Charles Lemoyne
Sunnybrook Research Institute
Kingston General Hospital
Investigators
Principal Investigator: Michael D Hill, MD,MSc FRCPC University of Calgary
Principal Investigator: Shelagh B Coutts, MD,FRCPC University of Calgary
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Michael Hill, PI, University of Calgary
ClinicalTrials.gov Identifier: NCT01654445     History of Changes
Other Study ID Numbers: Version 2.1, Oct 4,2012
Study First Received: July 25, 2012
Last Updated: February 18, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of Calgary:
Minor 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
Tenecteplase
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