TNK-tPA Evaluation for Minor Ischemic Stroke With Proven Occlusion

NCT ID: NCT01654445

Last Updated: 2020-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2014-07-31

Brief Summary

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.

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.

Conditions

Ischemic Stroke

Keywords

Minor stroke

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TNK-tPA Tenecteplase

This is an open-label trial, all patients will receive tenecteplase.

Group Type: EXPERIMENTAL

Tenecteplase

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

TNK-tPA

Eligibility 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)

NOTES: NIHSS = National Institutes of Health Stroke Scale ACA = anterior cerebral artery MCA = middle cerebral artery ICA = internal cerebral artery PCA = posterior cerebral artery VB = vertebrobasilar TICI = thrombolysis in cerebral ischemic scale CT = computed tomography NCCT = non-contrast CT CTA = CT angiography ASPECTS = Alberta Stroke Program Early CT Score IV = intravenous tPA = tissue plasminogen activator ED = Emergency Department

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vancouver General Hospital

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: collaborator

Hopital Charles Lemoyne

OTHER

Sponsor Role: collaborator

Université de Sherbrooke

OTHER

Sponsor Role: collaborator

Vancouver Island Health Authority

OTHER

Sponsor Role: collaborator

CHU de Quebec-Universite Laval

OTHER

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Dr. Michael Hill

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael D Hill, MD,MSc FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Shelagh B Coutts, MD,FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

University of Calgary

Calgary, Alberta, Canada

Countries

Canada

References

Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, Subramaniam S, Goyal M, Patil S, Menon BK, Barber PA, Dowlatshahi D, Field T, Asdaghi N, Camden MC, Hill MD; TEMPO-1 Investigators. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015 Mar;46(3):769-74. doi: 10.1161/STROKEAHA.114.008504. Epub 2015 Feb 12.

Reference Type: RESULT

PMID: 25677596 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.ucalgary.ca/dcns/research/clinical_trials/TEMPO-1

TEMPO-1 site

Other Identifiers

Version 2.2, Aug 28,2013

Identifier Type: -

Identifier Source: org_study_id