Study of Tenecteplase Versus Alteplase for Thrombolysis (Clot Dissolving) in Acute Ischemic Stroke

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.

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