Tenecteplase-Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke with Proven Occlusion

Shelagh B. Coutts, Véronique Dubuc, Jennifer Mandzia, Carol Kenney, Andrew M. Demchuk, Eric E. Smith, Suresh Subramaniam, Mayank Goyal, Shivanand Patil, Bijoy K. Menon, Philip A. Barber, Dar Dowlatshahi, Thalia Field, Negar Asdaghi, Marie Christine Camden, Michael D. Hill

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Background and Purpose: Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK-tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population. Methods: TNK-Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK-tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ≤5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0-1). Results: Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01-20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0-1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0-1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09-2.5; P=0.026). Conclusions: Administration of TNK-tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654445.

Original languageEnglish (US)
Pages (from-to)769-774
Number of pages6
Issue number3
StatePublished - Mar 1 2015
Externally publishedYes


  • Ischemic attack
  • Stroke
  • Therapeutic thrombolysis
  • Tomography
  • Transient
  • X-ray computed

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing


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