Study of Tenecteplase Versus Alteplase for Thrombolysis (Clot Dissolving) in Acute Ischemic Stroke (NOR-TEST)

Lars Thomassen

Status and phase

Completed

Phase 3

Conditions

Ischemic Stroke

Treatments

Drug: Tenecteplase

Drug: Alteplase

Study type

Interventional

Funder types

Other

Identifiers

NCT01949948

REK 2011/2435

Details and patient eligibility

About

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).

Full 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.

Enrollment

1,050 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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