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

July 25, 2012
February 18, 2013
July 2012
July 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01654445 on ClinicalTrials.gov Archive Site
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
Same as current
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
Same as current
 
TNK-tPA Evaluation for Minor Ischemic Stroke With Proven Occlusion
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Ischemic Stroke
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
Experimental: TNK-tPA Tenecteplase
This is an open-label trial, all patients will receive tenecteplase.
Intervention: Drug: Tenecteplase
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
July 2014
July 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact: Michael D Hill, MD 403-944-8065 michael.hill@ucalgary.ca
Contact: Shelagh B Coutts, MD 403-944-1594 scoutts@ucalgary.ca
Canada
 
NCT01654445
Version 2.1, Oct 4,2012
Yes
Dr. Michael Hill, University of Calgary
University of Calgary
  • Vancouver General Hospital
  • Ottawa Hospital Research Institute
  • University of Alberta
  • Hopital Charles Lemoyne
  • Sunnybrook Research Institute
  • Kingston General Hospital
Principal Investigator: Michael D Hill, MD,MSc FRCPC University of Calgary
Principal Investigator: Shelagh B Coutts, MD,FRCPC University of Calgary
University of Calgary
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP