TNK-tPA Evaluation for Minor Ischemic Stroke With Proven Occlusion

NCT01654445 | Completed Phase 2 Results DMC

• 1 other identifier: Version 2.2, Aug 28,2013
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke

Keywords

Minor stroke

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Serious Bleeding Events

  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.

  Up to 12 weeks

Secondary Outcomes (1)

• Number of Patients With NIHSS 0 and mRS 0 and Barthel Index > 90

  90 days

Other Outcomes (1)

• Number of Patients With Recanalization 4-8 Hours Post-treatment

  4-8 hours

Study Arms (1)

TNK-tPA Tenecteplase

EXPERIMENTAL

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

Drug: Tenecteplase

Interventions

Tenecteplase 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.

Also known as: TNK-tPA

TNK-tPA Tenecteplase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute ischemic stroke in an adult patient (18 years of age or older)
• Onset (last-seen-well) time to treatment time \< 12 hours.
• Minor stroke defined as a baseline NIHSS \< 6 at the time of randomization. Patients must have a demonstrable neurological deficit on physical neurological examination.
• 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.
• 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.
• Informed consent from the patient or surrogate.
• Patients can be treated within 90 minutes of the CT/CTA being completed.

You may not qualify if:

• 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.
• Large acute stroke \>1/3 MCA territory or ASPECTS\<5 visible on baseline CT scan.
• 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.
• Clinical history, past imaging and clinical judgment suggest that the intracranial occlusion is chronic.
• Patient is a candidate for and should receive standard of care IV tPA.
• 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.
• 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.
• 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.
• Pregnancy.
• Patient is actively taking dual antiplatelet medication (aspirin \& clopidogrel) in the last 48 hours.
• International normalized ratio \> 1.4
• 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

Sponsors & Collaborators

• University of Calgary: lead
• Vancouver General Hospital: collaborator
• Ottawa Hospital Research Institute: collaborator
• Hopital Charles Lemoyne: collaborator
• Université de Sherbrooke: collaborator
• Vancouver Island Health Authority: collaborator
• CHU de Quebec-Universite Laval: collaborator

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

Related Publications (1)

• 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.

  PMID: 25677596 RESULT

Related Links

• TEMPO-1 site

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tenecteplase; TNK-tissue plasminogen activator

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Limitations and Caveats

TEMPO-1 was a phase 2 study with a limited sample size. The program was designed to assess feasibility and safety and not efficacy. A further larger phase 3 study is planned. Only selected adverse events are presented here. All SAEs are reported.

Results Point of Contact

• Title: Shelagh B Coutts and Michael D Hill
• Organization: University of Calgary, Department of Clinical Neurosciences

michael.hill@ucalgary.ca

4039448065

Study Officials

• Michael D Hill, MD,MSc FRCPC

  University of Calgary

  PRINCIPAL INVESTIGATOR

• Shelagh B Coutts, MD,FRCPC

  University of Calgary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: July 25, 2012
• First Posted: July 31, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 25, 2020
• Results First Posted: November 25, 2020

Record last verified: 2020-11

Locations

CA (1)