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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
September 21, 2013
May 5, 2017
September 2012
December 31, 2016   (Final data collection date for primary outcome measure)
Clinical: Functional handicap [ Time Frame: 90 days ]
Excellent outcome defined as mRS 0-1
Functional handicap [ Time Frame: 90 days ]
modified Rankin Scale score (mRS) 0-1
Complete list of historical versions of study NCT01949948 on ClinicalTrials.gov Archive Site
  • 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
  • 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
  • Major neurological improvement [ Time Frame: 24 hours ]
    Reduction of ≥4 NIHSS (National Institutes of Health Stroke Scale) points compared with baseline (for patients with NIHSS ≥4 on admission)
Not Provided
Major neurological improvement [ Time Frame: 7 days ]
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
 
Study of Tenecteplase Versus Alteplase for Thrombolysis (Clot Dissolving) in Acute Ischemic Stroke
Randomised Trial of Tenecteplase vs. Alteplase for Recanalisation in Acute Ischemic Stroke

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).

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Outcomes Assessor
Primary Purpose: Treatment
Ischemic Stroke
  • Drug: Tenecteplase
    0.4 mg/kg single bolus intravenously
    Other Name: Metalyse
  • Drug: Alteplase
    0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously
    Other Name: Actilyse
  • Active Comparator: Tenecteplase
    0.4 mg/kg single bolus intravenously
    Intervention: Drug: Tenecteplase
  • Active Comparator: Alteplase
    0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously
    Intervention: Drug: Alteplase

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1050
December 31, 2016
December 31, 2016   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Norway
 
 
NCT01949948
REK 2011/2435
Yes
Not Provided
Not Provided
Not Provided
Lars Thomassen, Haukeland University Hospital
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
Haukeland University Hospital
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP