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

September 21, 2013
October 24, 2013
September 2012
June 2016   (final data collection date for primary outcome measure)
Functional handicap [ Time Frame: 90 days ] [ Designated as safety issue: No ]
modified Rankin Scale score (mRS) 0-1
Same as current
Complete list of historical versions of study NCT01949948 on ClinicalTrials.gov Archive Site
  • 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)
  • 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 NIHSS (National Institutes of Health Stroke Scale) points compared with baseline (for patients with NIHSS ≥4 on admission)
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
Same as current
 
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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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
Logallo N, Kvistad CE, Nacu A, Naess H, Waje-Andreassen U, Asmuss J, Aamodt AH, Lund C, Kurz MW, Rønning OM, Salvesen R, Idicula TT, Thomassen L. The Norwegian tenecteplase stroke trial (NOR-TEST): randomised controlled trial of tenecteplase vs. alteplase in acute ischaemic stroke. BMC Neurol. 2014 May 15;14:106. doi: 10.1186/1471-2377-14-106.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
954
September 2016
June 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 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
Both
18 Years and older
No
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
Norway
 
NCT01949948
REK 2011/2435
Yes
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
October 2013

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