This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Study of Tenecteplase Versus Alteplase for Thrombolysis (Clot Dissolving) in Acute Ischemic Stroke (NOR-TEST)

This study has been completed.
Sponsor:
Collaborator:
The Research Council of Norway
Information provided by (Responsible Party):
Lars Thomassen, Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT01949948
First received: September 21, 2013
Last updated: May 5, 2017
Last verified: May 2017
  Purpose

BACKGROUND: Alteplase dissolves blood vessel clots in acute ischemic stroke and is the only approved acute drug treatment <4½ hours of stroke onset. The overall benefit from alteplase is substantial, but up to 2/3 of patients with large artery clots may not achieve reopening of the vessel and up to 40% of the patients may remain severely disabled or die, leaving substantial room for improvement. Tenecteplase, widely used in coronary heart disease, may be more effective and may have less bleeding complications than alteplase, and may be the drug of choice also in stroke.

HYPOTHESIS: Tenecteplase may be given safely to patients with acute ischemic stroke at a dose that is associated with improved clinical outcome compared with existing treatment options.

AIMS: To compare efficacy and safety of tenecteplase vs. alteplase given <4½ hours after symptom onset.

STUDY ENDPOINTS: The primary study endpoint is excellent clinical outcome at 3 months (effect). Secondary study endpoints are major early clinical improvement (effect) and bleeding complications (safety).


Condition Intervention Phase
Ischemic Stroke Drug: Tenecteplase Drug: Alteplase Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomised Trial of Tenecteplase vs. Alteplase for Recanalisation in Acute Ischemic Stroke

Resource links provided by NLM:


Further study details as provided by Lars Thomassen, Haukeland University Hospital:

Primary Outcome Measures:
  • Clinical: Functional handicap [ Time Frame: 90 days ]
    Excellent outcome defined as mRS 0-1


Secondary Outcome Measures:
  • Symptomatic cerebral hemorrhage [ Time Frame: 24-36 hours ]
    Haemorrhagic transformation (haemorrhagic infarct / haematoma) as defined by CT (or MRI)

  • Hemorrhagic transformation [ Time Frame: 24-36 hours ]
    Any hemorrhagic infarct or parenchymal hematoma

  • Neurological improvement [ Time Frame: 24 hours ]
    NIHSS changes from baseline: NIHSS=0 or reduction of ≥4 NIHSS points

  • Clinical: Functional handicap [ Time Frame: 90 days ]
    Ordinal shift analysis of mRS

  • Safety [ Time Frame: 90 days ]
    Death


Enrollment: 1050
Actual Study Start Date: September 2012
Study Completion Date: December 31, 2016
Primary Completion Date: December 31, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tenecteplase
0.4 mg/kg single bolus intravenously
Drug: Tenecteplase
0.4 mg/kg single bolus intravenously
Other Name: Metalyse
Active Comparator: Alteplase
0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously
Drug: Alteplase
0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously
Other Name: Actilyse

Detailed Description:

HYPOTHESIS: 1) Tenecteplase 0.4 mg/kg may be given safely to patients with acute ischaemic stroke <4½ hours after stroke onset. 2) Tenecteplase 0,4 mg/kg (single bolus)has superior efficacy and safety compared with alteplase 0.9 mg/kg (10% bolus + 90% infusion/60 minutes) when given within 4 ½ hours after stroke onset.

DESIGN: NOR-TEST is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial with randomisation tenecteplase:alteplase 1:1.

POWER CALCULATION: NOR-TEST aims at detecting a 9 % higher percentage excellent outcome with tenecteplase vs. alteplase (r1=0.40; r2=0.49; OR 1.44; power 0.8), and will include 954 patients during 3 years.

PATIENT RECRUITMENT: All patients found eligible for thrombolytic therapy are eligible for NOR-TEST, i.e. NOR-TEST changes neither inclusion nor exclusion criteria. The number of patients treated at a participating centre will therefore essentially remain unchanged. Estimated 400 patients are thrombolysed per year in participating centres. Allowing for 20% of patients not being included in NOR-TEST, the total number of patients (n=954) will still be met.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Ischaemic stroke with measurable deficit on NIH Stroke Scale
  • All stroke sub-types, severities and vascular distributions,a visible arterial occlusion is not required for inclusion
  • Treatment within 4 ½ hours of stroke onset
  • Patients awakening with symptoms are defined by the time last observed normal and awake
  • Informed written consent signed by the patient, verbal consent from the patients as witnessed by a non-participating health care person, or consent by the signature of the patient's family must be provided

Exclusion Criteria:

  • Patients with premorbid modified Rankin Scale (mRS) score ≥3
  • Patients for whom a complete NIH Stroke Score cannot be obtained
  • Hemiplegic migraine with no arterial occlusion on CTA
  • Seizure at stroke onset and no visible occlusion on baseline CTA
  • Intracranial haemorrhage on baseline CT
  • Clinical presentation suggesting subarachnoid haemorrhage even if baseline CT is normal
  • Large areas of hypodense ischaemic changes on baseline CT
  • Patients with systolic blood pressure >185 mm Hg or diastolic blood pressure >110 mm Hg
  • Female, pregnant or breast feeding
  • Known bleeding diathesis
  • Use of oral anticoagulants and International Normalized Ratio (INR) ≥1,4
  • Use of new oral anticoagulants (NOAC) within the last 12 hours
  • Heparin <48 hours and increased Activated partial thromboplastin tike (APTT)
  • Low molecular weight heparin(oid) <24 hours
  • Any other investigational drug <14 days
  • Sepsis
  • Patients with arterial puncture at a noncompressible site or lumbar puncture <7 days
  • Major surgery or serious trauma <14 days
  • Gastrointestinal or urinary tract hemorrhage <14 days
  • Clinical stroke <2 months
  • History of intracranial haemorrhage
  • Brain neurosurgery <2 months
  • Serious head trauma <2 months
  • Pericarditis
  • Any serious medical illness likely to interact with treatment
  • Confounding pre-existent neurological or psychiatric disease
  • Unlikely to complete follow-up
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01949948

Locations
Norway
Haukeland University Hospital
Bergen, Norway, 5021
Nordland Hospital
Bodø, Norway, 8092
Drammen Hospital
Drammen, Norway, 3004
Førde Central Hospital
Førde, Norway, 6800
Haugesund Hospital
Haugesund, Norway, 5516
Molde Hospital
Molde, Norway, 6400
Akershus University Hospital
Nordbyhagen, Norway, 1474
Ullevål University Hospital
Oslo, Norway, 0424
Baerum Hospital
Rud, Norway, 1309
Telemark Hospital
Skien, Norway, 3710
Stavanger University Hosital
Stavanger, Norway, 4017
St. Olav Hospital NTNU
Trondheim, Norway, 7006
Tønsberg Hospital
Tønsberg, Norway, 3100
Sponsors and Collaborators
Lars Thomassen
The Research Council of Norway
Investigators
Study Chair: Lars Thomassen, MD PhD Prof. Dept. Neurology, Haukeland University HospitalBergen, Norway
Study Director: Ulrike Waje-Andreassen, MD PhD Prof. Dept. Neurology, Haukeland University Hospital, Bergen
Principal Investigator: Nicola Logallo, MD PhD Dept. Neurology, Haukeland University Hospital, Bergen, Norway
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lars Thomassen, Senior Consultant neurologist; Professor, Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT01949948     History of Changes
Other Study ID Numbers: REK 2011/2435
Study First Received: September 21, 2013
Last Updated: May 5, 2017

Keywords provided by Lars Thomassen, Haukeland University Hospital:
treatment, intervention, thrombolysis

Additional relevant MeSH terms:
Stroke
Ischemia
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Tissue Plasminogen Activator
Tenecteplase
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 21, 2017