Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Haukeland University Hospital
The Research Council of Norway
Information provided by (Responsible Party):
Lars Thomassen, Haukeland University Hospital Identifier:
First received: September 21, 2013
Last updated: September 9, 2016
Last verified: September 2016

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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 Haukeland University Hospital:

Primary Outcome Measures:
  • Proof of concept: Neurological improvement [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    NIHSS changes from baseline: NIHSS=0 or reduction of ≥4 NIHSS points compared with baseline

  • Clinical: Functional handicap [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Sliding dichotomy/responder analysis: Excellent outcome defined as mRS 0 with baseline NIHSS ≤7, as mRS 0-1 with baseline NIHSS 8-14, as mRS 0-2 with baseline NIHSS ≥15

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

  • Hemorrhagic transformation [ Time Frame: 24-36 hours ] [ Designated as safety issue: Yes ]
    Any hemorrhagic infarct or parenchymal hematoma

  • Infarct volume and location(s) [ Time Frame: 24-36 hours ] [ Designated as safety issue: No ]
    MRI Infarct volume and ASPECTS score

Other Outcome Measures:
  • Early clinical outcome [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Sliding dichotomy/responder analysis: Excellent outcome is defined as mRS 0 with baseline NIHSS ≤7, as mRS 0-1 with baseline NIHSS 8-14, as mRS 0-2 with baseline NIHSS ≥15

Estimated Enrollment: 954
Study Start Date: September 2012
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: December 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 identifier: NCT01949948

Contact: Lars Thomassen, MD PhD Prof +47 55 97 50 00
Contact: Nicola Logallo, MD PhD +47 55 97 50 00

Haukeland University Hospital Recruiting
Bergen, Norway, 5021
Contact: Ulrike Waje-Andreassen, MD PhD Prof    +47 55 97 50 00   
Contact: Lars Thomassen, MD PhD Prof    +47 55 97 50 00   
Principal Investigator: Nicola Logallo, MD PhD         
Nordland Hospital Recruiting
Bodø, Norway, 8092
Contact: Maria Carlsson, MD    +47 75 53 40 00   
Principal Investigator: Maria Carlsson, MD         
Drammen Hospital Recruiting
Drammen, Norway, 3004
Contact: Karl F Amthor, MD    +47 32803693   
Principal Investigator: Karl F Amthor, MD         
Førde Central Hospital Recruiting
Førde, Norway, 6800
Contact: Magdalena Stankiewicz-Pietrzak, MD    57839000   
Principal Investigator: Magdalena Stankiewicz-Pietrzak, MD         
Haugesund Hospital Recruiting
Haugesund, Norway, 5516
Contact: kamal Kahlon, MD    52732000   
Principal Investigator: Kamal Kahlon, MD         
Molde Hospital Recruiting
Molde, Norway, 6400
Contact: Åse Hagen Morsund, MD    +47 71120000   
Principal Investigator: Åse H Morsund, MD         
Akershus University Hospital Recruiting
Nordbyhagen, Norway, 1474
Contact: Bente Thommessen, MD PhD    +47 67 92 88 00   
Principal Investigator: Bente Thommessen, MD         
Ullevål University Hospital Recruiting
Oslo, Norway, 0424
Contact: Lars H Alteheld, MD    +42 22118080   
Principal Investigator: Lars H Alteheld, MD         
Baerum Hospital Recruiting
Rud, Norway, 1309
Contact: Hege Ihle-Hansen, MD PhD    +4741443866   
Telemark Hospital Recruiting
Skien, Norway, 3710
Contact: Håkon Tobro, MD    +4735003500   
Principal Investigator: Håkon Tobro, MD         
Stavanger University Hosital Recruiting
Stavanger, Norway, 4017
Contact: Martin Kurz, MD PhD    +47 51518426   
Principal Investigator: Martin Kurz, MD PhD         
St. Olav Hospital NTNU Recruiting
Trondheim, Norway, 7006
Contact: Titto T Idicula, MD PhD    +47 06800   
Principal Investigator: Titto T Idicula, MD PhD         
Tønsberg Hospital Recruiting
Tønsberg, Norway, 3100
Contact: Reidar Kloster, MD    +47 33 32 44 46   
Principal Investigator: Reidar Kloster, MD         
Sponsors and Collaborators
Lars Thomassen
The Research Council of Norway
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 automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Lars Thomassen, Senior Consultant neurologist; Professor, Haukeland University Hospital Identifier: NCT01949948     History of Changes
Other Study ID Numbers: REK 2011/2435 
Study First Received: September 21, 2013
Last Updated: September 9, 2016
Health Authority: Norway: Norwegian Medicines Agency

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

Additional relevant MeSH terms:
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
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action processed this record on October 21, 2016