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.
- Tenecteplase (TNKase)Drug
Other Names: Metalyse Intervention Desc: 0.4 mg/kg single bolus intravenously ARM 1: Kind: Experimental Label: Tenecteplase Description: 0.4 mg/kg single bolus intravenously
- Alteplase Drug
Intervention Desc: 0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously ARM 1: Kind: Experimental Label: Alteplase Description: 0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously
- Allocation: Randomized
- Masking: Double Blind (Subject, Outcomes Assessor)
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||Functional handicap||90 days||No|
|Secondary||Symptomatic cerebral hemorrhage||24-36 hours||Yes|
|Secondary||Hemorrhagic transformation||24-36 hours||Yes|
|Secondary||Major neurological improvement||24 hours||No|
|Primary||Proof of concept: Neurological improvement||24 hours||No|
|Primary||Clinical: Functional handicap||90 days||No|
|Secondary||Infarct volume and location(s)||24-36 hours||No|
|Secondary||Neurological improvement||24 hours|