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 October 2013 by Haukeland University Hospital
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: October 24, 2013
Last verified: October 2013
  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
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:
  • Functional handicap [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    modified Rankin Scale score (mRS) 0-1


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

  • Major neurological improvement [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Reduction of ≥4 points on the National Institutes of Health Stroke Scale (NIHSS) compared with baseline (for patients with NIHSS ≥4 on admission)


Other Outcome Measures:
  • Major neurological improvement [ 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: September 2016
Estimated Primary Completion Date: June 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
Genders Eligible for Study:   Both
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 before treatment

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 baseline CT
  • Seizure at stroke onset and no visible occlusion on baseline CT
  • 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 primary endovascular treatment
  • 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
  • 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

Contacts
Contact: Lars Thomassen, MD PhD Prof +47 55 97 50 00 ltho@haukeland.no
Contact: Nicola Logallo, MD PhD +47 55 97 50 00 nalo@helse-bergen.no

Locations
Norway
Haukeland University Hospital Recruiting
Bergen, Norway, 5021
Contact: Ulrike Waje-Andreassen, MD PhD Prof    +47 55 97 50 00    uwan@haukeland.no   
Contact: Lars Thomassen, MD PhD Prof    +47 55 97 50 00    ltho@haukeland.no   
Principal Investigator: Nicola Logallo, MD PhD         
Nordland Hospital Active, not recruiting
Bodø, Norway, 8092
Drammen Hospital Recruiting
Drammen, Norway, 3004
Contact: Karl F Amthor, MD    +47 32803693    Karl-Friedrich.Amthor@vestreviken.no   
Principal Investigator: Karl F Amthor, MD         
Østfold Hospital Fredrikstad Active, not recruiting
Fredrikstad, Norway, 1639
Førde Central Hospital Recruiting
Førde, Norway, 6800
Contact: Magdalena Stankiewicz-Pietrzak, MD    57839000    magdalena.stankiewicz@helse-forde.no   
Principal Investigator: Magdalena Stankiewicz-Pietrzak, MD         
Haugesund Hospital Active, not recruiting
Haugesund, Norway, 5516
Molde Hospital Not yet recruiting
Molde, Norway, 6400
Contact: Åse Hagen Morsund, MD    +47 71120000    Ase.hagen.morsund@helse-mr.no   
Principal Investigator: Åse H Morsund, MD         
Akershus University Hospital Active, not recruiting
Nordbyhagen, Norway, 1474
Ullevål University Hospital Active, not recruiting
Oslo, Norway, 0424
Telemark Hospital Active, not recruiting
Skien, Norway, 3710
Stavanger University Hosital Active, not recruiting
Stavanger, Norway, 4017
St. Olav Hospital NTNU Active, not recruiting
Trondheim, Norway, 7006
Tønsberg Hospital Recruiting
Tønsberg, Norway, 3100
Contact: Reidar Kloster, MD    +47 33 32 44 46    reidar.kloster@siv.no   
Principal Investigator: Reidar Kloster, MD         
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

No publications provided by Haukeland University Hospital

Additional 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: October 24, 2013
Health Authority: Norway: Norwegian Medicines Agency

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

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

ClinicalTrials.gov processed this record on July 23, 2014