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

Sponsor

Lars Thomassen (Other)

Overall Status

Completed

CT.gov ID

NCT01949948

Collaborator

The Research Council of Norway (Other)

1,050

Enrollment

Locations

Arms

Actual Duration (Months)

80.8

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: Tenecteplase Drug: Alteplase	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1050 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomised Trial of Tenecteplase vs. Alteplase for Recanalisation in Acute Ischemic Stroke

Actual Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Dec 31, 2016

Actual Study Completion Date :

Dec 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tenecteplase 0.4 mg/kg single bolus intravenously	Drug: Tenecteplase 0.4 mg/kg single bolus intravenously Other Names: Metalyse
Active Comparator: Alteplase 0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously	Drug: Alteplase 0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously Other Names: Actilyse

Arm

Intervention/Treatment

Active Comparator: Tenecteplase

0.4 mg/kg single bolus intravenously

Drug: Tenecteplase

0.4 mg/kg single bolus intravenously

Other Names:

Metalyse

Active Comparator: Alteplase

0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously

Drug: Alteplase

0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously

Other Names:

Actilyse

Outcome Measures

Primary Outcome Measures

Clinical: Functional handicap [90 days]
Excellent outcome defined as mRS 0-1

Secondary Outcome Measures

Symptomatic cerebral hemorrhage [24-36 hours]
Haemorrhagic transformation (haemorrhagic infarct / haematoma) as defined by CT (or MRI)
Hemorrhagic transformation [24-36 hours]
Any hemorrhagic infarct or parenchymal hematoma
Neurological improvement [24 hours]
NIHSS changes from baseline: NIHSS=0 or reduction of ≥4 NIHSS points
Clinical: Functional handicap [90 days]
Ordinal shift analysis of mRS
Safety [90 days]
Death

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Haukeland University Hospital	Bergen	Norway	5021
2	Nordland Hospital	Bodø	Norway	8092
3	Drammen Hospital	Drammen	Norway	3004
4	Førde Central Hospital	Førde	Norway	6800
5	Haugesund Hospital	Haugesund	Norway	5516
6	Molde Hospital	Molde	Norway	6400
7	Akershus University Hospital	Nordbyhagen	Norway	1474
8	Ullevål University Hospital	Oslo	Norway	0424
9	Baerum Hospital	Rud	Norway	1309
10	Telemark Hospital	Skien	Norway	3710
11	Stavanger University Hosital	Stavanger	Norway	4017
12	St. Olav Hospital NTNU	Trondheim	Norway	7006
13	Tønsberg Hospital	Tønsberg	Norway	3100

Sponsors and Collaborators

Lars Thomassen
The Research Council of Norway

Investigators

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