title: Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01654445.
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.). scoutts@ucalgary.ca.
authors: Shelagh B
authors: SB
authors: Coutts
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Véronique
authors: V
authors: Dubuc
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Jennifer
authors: J
authors: Mandzia
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Carol
authors: C
authors: Kenney
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Andrew M
authors: AM
authors: Demchuk
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Eric E
authors: EE
authors: Smith
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Suresh
authors: S
authors: Subramaniam
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Mayank
authors: M
authors: Goyal
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Shivanand
authors: S
authors: Patil
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Bijoy K
authors: BK
authors: Menon
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Philip A
authors: PA
authors: Barber
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Dar
authors: D
authors: Dowlatshahi
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Thalia
authors: T
authors: Field
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Negar
authors: N
authors: Asdaghi
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Marie-Christine
authors: MC
authors: Camden
authors: From the Calgary Stroke Program, Departments of Clinical Neurosciences (S.B.C., V.D., J.M., C.K., A.M.D., E.E.S., S.S., M.G., B.K.M., P.A.B., M.D.H.), Radiology (S.B.C., A.M.D., E.E.S., M.G., S.P., B.K.M., M.D.H.), Community Health Sciences (E.E.S., M.D.H.), and Medicine (M.D.H.), and Hotchkiss Brain Institute (S.B.C., A.M.D., E.E.S., M.G., B.K.M., P.A.B., M.D.H.), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (D.D.); Vancouver Stroke Program, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada (T.F., N.A.); and Department of Neurosciences, Enfant-Jésus Hospital, Laval University, Quebec City, Quebec, Canada (M.-C.C.).
authors: Michael D
authors: MD
authors: Hill
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy*; D002170:Canada; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy*; D000077785:Tenecteplase; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase
keywords: ischemic attack, transient; stroke; therapeutic thrombolysis; tomography, x-ray computed